@article{Wang2016,
   author = {Wang, Sijia and Hüttmann, Gereon and Rudnitzki, Florian and Diddens-Tschoeke, Heyke and Zhang, Zhenxi and Rahmanzadeh, Ramtin},
   title = {Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy},
   journal = {Journal of Biomedical Optics},
   volume = {21},
   number = {7},
   pages = {078001-078001},
   note = {10.1117/1.JBO.21.7.078001},
   abstract = {Abstract.  The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.},
   ISSN = {1083-3668},
   year = {2016},
   type = {Journal Article}
}

@article{Diddens-Tschoeke2015,
   author = {Diddens-Tschoeke, Heyke C. and Hüttmann, Gereon and Gruber, Achim D. and Pottier, Roy H. and Hanken, Henning},
   title = {Localized thermal tumor destruction using dye-enhanced photothermal tumor therapy},
   journal = {Lasers in Surgery and Medicine},
   pages = {n/a-n/a},
   keywords = {photothermal therapy
naphthalocyanine derivative
in-vivo
laser
dye-enhanced},
   ISSN = {1096-9101},
   DOI = {10.1002/lsm.22356},
   url = {http://dx.doi.org/10.1002/lsm.22356},
   year = {2015},
   type = {Journal Article}
}

@article{Kantelhardt,
   author = {Kantelhardt, S.R. and Diddens, H. and Leppert, J. and Rohde, V. and Hüttmann, G. and Giese, A.},
   title = {Multiphoton excited fluorescence microscopy of 5-ALA induced fluorescence in exprimental},
   journal = {Laser Surg Med},
   volume = {40
},
   number = {4},
   pages = {273-81},
   year = {2008}
}

@article{Löning,
   author = {Löning, M. and Lankenau, E. and Diddens, H. and Krokowski, M. and Diedrich, K. and Hüttmann, G.},
   title = {Optische Kohärenztomographie in der Gynokologie},
   journal = {Der Gynäkologe},
   volume = {40},
   number = {5},
   year = {2007}
}

@article{Diddens,
   author = {Diddens, H. and Arp, N. and Eisenbeiß, W.},
   title = {Photodynamische Therapie zur Behandlung lokaler Wunden},
   journal = {GMS Krankenhaushyg Interdiszip},
   volume = {1},
   number = {1},
   pages = {Doc 19},
   year = {2006}
}

@article{Löning,
   author = {Löning, M. and Diddens, H. and W, Küpker and Diedrich, K. and Hüttmann, G.},
   title = {Laparoscopic Fluorescence Detection of Ovarian Carcinoma Metastases Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX},
   journal = {CANCER},
   volume = {100},
   number = {8},
   year = {2004}
}

@article{Diddens,
   author = {Diddens, H. and Fischer, F. and Pottier, R. H.},
   title = {In-vivo investigations on dye-enhanced photothermal tumor therapy with a naphthalocyanine derivative},
   journal = {Oftalmologia},
   volume = {56},
   number = {1},
   pages = {59-61},
   note = {Diddens, Heyke
Fischer, Frank
Pottier, Roy H
Romania
Bucharest, Romania : 1990
Oftalmologia. 2003;56(1):59-61.},
   abstract = {Chromophore-enhanced photothermal therapy involves the application of an exogenous chromophore in combination with irradiation, using an appropriate wavelength, exposure duration and sufficient irradiances. The chromophore palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8) accumulates at satisfactory concentrations and with good selectivity between both tumor and muscle and tumor and skin in tumor-bearing mice. In an attempt to thermally damage tumor tissue with concurrent sparing of adjacent normal tissue, the potential of PdNc(OBu)8 for photothermal therapy was investigated. Using a Balb/c mouse model with subcutaneously implanted EMT6 adenocarcinoma, 90-100 hours after intraperitoneal application of PdNc(OBu)8, the tumor and surrounding tissue were irradiated with a 826nm continuous-wave diode laser. The thermal effects on tumor and normal tissue were evaluated histologically. Our results indicate that after PdNc(OBu)8 administration and tumor irradiation using 5W/cm-for 100 seconds, pronounced selective heating of the tumor was achieved in mice, while in control animals merely an unspecific and marginal overall increase in temperature over the entire irradiation area was observed. Histological evaluation of treated areas indicated that the PdNc(OBu)8-targeted tumor tissue showed severe thermal damage while peripheral tissue like skin and muscle remained largely unaffected. This study shows the potential of creating localized thermal effects by using PdNc(OBu)8 and continuous-wave light for chromophore-enhanced photothermal therapy.},
   keywords = {Adenocarcinoma/*therapy
Animals
Disease Models, Animal
Female
Hindlimb
Lasers
Mice
Mice, Inbred BALB C
Organometallic Compounds/*therapeutic use
Photochemotherapy/*methods
Soft Tissue Neoplasms/*therapy
Treatment Outcome},
   year = {2003}
}

@misc{Hüttmann,
   author = {Hüttmann, G and Houserek, S. and Diddens, H. and Hendrich, C.},
   title = {Photodynamische Therapie in der Orthopädie},
   pages = {344-352},
   year = {2002}
}

@article{Noske,
   author = {Noske, U.M. and Schmidt-Erfurth, U. and Meyer, C. and Diddens, H.},
   title = {Lipidmetabolismus im Retinalen Pigmentepithel (RPE): Mögliche Bedeutung der Lipoprotein-Rezeptoren bei der Altersbezogenen Makuladegeneration},
   journal = {Ophthalmologe},
   volume = {95},
   pages = {814-819},
   year = {1998}
}

@article{Hendrich,
   author = {Hendrich, C. and Hüttmann, G. and Lehnert, C. and Diddens, H. and Siebert, W.E.},
   title = {Photodynamic laser therapy for rheumatoid arthritis: Cell culture studies and animal experiments.},
   journal = {Knee Surg Sports Traumatol Arthroscopy},
   volume = {5},
   pages = {58-63},
   year = {1997}
}

@article{Schmidt-Erfurth1997,
   author = {SchmidtErfurth, U. and Diddens, H. and Birngruber, R. and Hasan, T.},
   title = {Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates},
   journal = {British Journal of Cancer},
   volume = {75},
   number = {1},
   pages = {54-61},
   note = {Wa344
Times Cited:69
Cited References Count:64},
   abstract = {Combination of photosensitizers with carrier molecules has been shown to enhance the efficiency of photodynamic therapy (PDT). Owing to an increased expression of their receptors on some malignant and proliferating cells, low-density lipoproteins (LDLs) are potential endogenous carriers. A photosensitizer, chlorin e(6) (Ce-6), was covalently bound to LDL via carbodiimide activation. The Ce-6-LDL conjugate was evaluated on a fibroblast cell line with defined LDL receptor expression and a retinoblastoma cell line (Y79). Uptake of free Ce-6 and Ce-6 either covalently bound to or complexed with LDL was measured by spectrofluorimetry. Phototoxicity after irradiation at 660 nm was determined by a mitochondrial activity assay (MTT). Covalent binding to LDL significantly increased the uptake of Ce, for both cell lines by a factor of 4-5. A Ce-6:LDL binding ratio of 50:1 was optimal. A receptor-mediated uptake was demonstrated by saturability and competitive inhibition by free LDL. Binding also occurred at 2 degrees C and was attributed to non-specific associations. Irradiation with 10 J cm(-2) of 660 nm light after treatment of cells with Ce-6-LDL conjugate reduced the MTT activity by 80%, while free or mixed Ce-6 induced a maximum of 10% reduction in the MTT activity following identical treatment conditions. These data suggest that targeting of LDL receptor-bearing cells using covalently bound carriers, such as LDL, might increase the efficiency and selectivity of PDT. Intraocular tumours such as retinoblastomas could be appropriate targets for such an approach owing to the ease of access of light sources and the need for non-invasive approaches in sensitive ocular sites.},
   keywords = {photochemistry
ocular
neovascularization
chlorin
bladder-carcinoma cells
receptor-mediated uptake
plasma-lipoproteins
endothelial-cells
human fibroblasts
cellular-uptake
therapy
tumor
benzoporphyrin
cancer},
   ISSN = {0007-0920},
   DOI = {Doi 10.1038/Bjc.1997.9},
   url = {<Go to ISI>://WOS:A1997WA34400009},
   year = {1997},
   type = {Journal Article}
}

@inproceedings{Hüttmann1,
   author = {Hüttmann, G. and Hendrich, C. and Birngruber, R. and Lehnert, C. and Seara, J. and Siebert, W. E. and Diddens, H.},
   title = {Protoporphyrin IX distribution after intra-articular and systemic application of 5-aminolevulinic acid in healthy and arthritic joints . 
Mechanisms and Techniques in Photodynamic Therapy V,},
   booktitle = {Proc. SPIE},
   volume = {2675},
   pages = {238-242},
Year = { 1996}

}

@inproceedings{Hüttmann,
   author = {Hüttmann, G. and Achtelik, W. and Löning, M. and Sommer, K. and Diddens, H.},
   title = {Fluorescence microscopy studies on ALA sensitized tissues},
   booktitle = {SPIE Proc.},
   volume = {2926},
   pages = {24-31},
year = { 1996},
URL = {  https://doi.org/10.1117/12.260815}

}

@article{Gillies,
   author = {Gillies, R. and Kollias, N. and Hasan, T. and Diddens, H.},
   title = {Spectral characterization of the benzoporphyrin derivative monoacid ring-A photoproduct formed in fetal calf solutions during irradiation with 694 nm continuous-wave radiation},
   journal = {J Photochem Photobiol B},
   volume = {33},
   number = {1},
   pages = {87-90},
   abstract = {Benzoporphyrin derivative monoacid ring A (BPD-MA) is a second-generation photosensitizer for photodynamic therapy (PDT) that has shown good results in phase I clinical trials. Similar to other porphyrin derivatives, BPD-MA readily photobleaches during in-vivo PDT treatment. This study investigated the photodegradation of BPD-MA in fetal calf serum (FCS) solutions in vitro. Absorption and fluorescence spectra from dilute solutions of BPD-MA in 10% FCS were recorded before and immediately after irradiation with light at 694 nm. After irradiation, the appearance of a new fluorescence emission band at 650 nm and changes in the fluorescence excitation spectra indicate the formation of a photoproduct. Photoproduct formation was observed only when BPD-MA was bound to FCS and in oxygenated solutions. The spectroscopy of the photoproduct is consistent with the reaction of an oxygen species with the ring B vinyl group, forming a hydroxyaldehyde photoproduct. Monitoring the increase in photoproduct fluorescence during treatment may provide an in-vivo dosimeter to measure PDT efficacy.},
   year = {1996}
}

@article{Novo,
   author = {Novo, M. and Hüttmann, G. and Diddens, H.},
   title = {Chemical instability of 5-aminolevulinic acid used in the fluorescence diagnosis of bladder tumours},
   journal = {J Photoch Photobio},
   volume = {34},
   pages = {143-148},
   year = {1996}
}

@article{Reichle,
   author = {Reichle, A. and Diddens, H. and Altmayr, F. and Rastetter, J. and Andreesen, R.},
   title = {Beta-tubulin and P-glycoprotein: Major determinants of vincristine accumulation in B-CLL cells},
   journal = {Leuk Res},
   volume = {19},
   number = {11},
   pages = {823-829},
   abstract = {Vincristine (VCR) accumulation in chronic lymphatic leukemia of B-cell origin (B-CLL) has recently been shown not to be inversely correlated to P-glycoprotein (PGP) levels. Therefore, we studied, in addition to PGP expression and accumulation of VCR, the cellular ?-tubulin content in quiescent and rhIL-2 activated B-CLL cells. VCR mediates cytotoxicity by binding to tubulin. Constitutive ?-tubulin levels in B-CLL cells varied considerably. Upon activation with rhIL-2, ?-tubulin expression increased significantly. Therefore, tubulin levels could be correlated over a wide range to VCR accumulation. When the PGP-mediated drug efflux was blocked by verapamil (VRP), tubulin levels correlated linearly to VCR accumulation. All B-CLL cases expressed PGP at different levels. There was no linear correlation between PGP expression and VCR accumulation. A modulation factor m was defined as a quotient of VCR accumulation in the presence and absence of VRP to define the extent by which VRP inhibited a steady-state accumulation of VCR. The factor allowed discrimination between B-CLLs expressing low versus high PGP, irrespective of the levels of tubulin. However, PGP and ?-tubulin levels together were predictive for VCR accumulation in steady state. There was no uniform accumulation defect for VCR in B-cell CLL because ?-tubulin and PGP were expressed independently. Non PGP-mediated VCR transport seems to play a minor role in B-cell CLL. Leukemia-associated varying of cytoskeletal organization in B-cell CLL might be one reason for the diverse cellular responses to receptor-mediated signals.},
   keywords = {Multidrug resistance
tubulin
vincristine
B-CLL},
   year = {1995}
}

@article{Schmidt-Erfurth1994,
   author = {Schmidt Erfurth, U. and Diddens, H. and Bamberg, M. and Birngruber, R. and Hasan, T.},
   title = {Carrier-Mediated Targeting in Photodynamic Therapy of Retinoblastoma Cells},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {35},
   number = {4},
   pages = {2119-2119},
   note = {Mz585
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1994MZ58504004},
   year = {1994},
   type = {Journal Article}
}

@article{Reichle,
   author = {Reichle, A. and Diddens, H. and Altmayr, F. and Rastetter, J. and Andreesen, R.},
   title = {Chemomodulation of drugs involved in multiple resistance in chronic lymphatic leukemia of the B-cell type},
   journal = {Cancer Chemother Pharmacol.
},
   volume = {34},
   number = {4},
   pages = {307-16},
   year = {1994}
}

@article{Gekeler,
   author = {Gekeler, V. and Frese, G. and Noller, A. and Handgretinger, R. and Wilisch, A. and Schmidt, H. and Muller, C. P. and Dopfer, R. and Klingebiel, T. and Diddens, H. and et al.},
   title = {Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemias},
   journal = {Br J Cancer},
   volume = {66},
   number = {3},
   pages = {507-17},
   note = {Gekeler, V
Frese, G
Noller, A
Handgretinger, R
Wilisch, A
Schmidt, H
Muller, C P
Dopfer, R
Klingebiel, T
Diddens, H
Research Support, Non-U.S. Gov't
England
Br J Cancer. 1992 Sep;66(3):507-17.},
   abstract = {In a variety of adult and childhood leukaemia cell samples collected at different states of the disease, we analysed in a series of sequentially performed slot-blot or Northern-blot hybridisation experiments the expression of genes possibly involved in multiple drug resistance (MDR) (mdr1/P-glycoprotein, DNA topoisomerase II, glutathione-S-transferase pi), and the expression of the DNA topoisomerase I and histone 3.1 genes. Occasionally, P-glycoprotein gene expression was additionally examined by indirect immunocytofluorescence using the monoclonal antibody C219. No significant difference in mdr1/P-glycoprotein mRNA levels between primary and relapsed state acute lymphocytic leukaemias (ALL) was seen on average. Second or third relapses, however, showed a distinct tendency to an elevated expression of this multidrug transporter gene (up to 10-fold) in part well beyond the value seen in the moderately cross-resistant T-lymphoblastoid CCRF-CEM subline CCRF VCR 100. Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years. Topoisomerase I and topoisomerase II mRNA levels were found to be very variable. Whereas in all but one case of CLL topoisomerase II mRNA was not detected by slot-blot hybridizations, strong topoisomerase I and topoisomerase II gene expression levels, frequently exceeding the levels monitored in the CCRF-CEM cell line, were seen in many cell samples of acute leukaemia. If topoisomerase II mRNA was undetectable, expression of topoisomerase I was clearly visible throughout. These observations might be valuable considering the possible treatment with specific topoisomerase I or topoisomerase II inhibitors. Significant positive correlations were found (i) for topoisomerase I and histone 3.1 gene expression levels in general (P less than 0.001), and (ii) in the CLL samples additionally for the expression levels of the mdr1 gene, and the histone 3.1, topoisomerase I, and glutathione-S-transferase pi genes, respectively.},
   keywords = {Adult
Child
DNA Probes
DNA Topoisomerases, Type I/ genetics
DNA Topoisomerases, Type II/ genetics
Drug Resistance/ genetics
Fluorescent Antibody Technique
Gene Expression/ genetics
Glutathione Transferase/ genetics
Histones/ genetics
Humans
Leukemia/drug therapy/ genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
Leukemia, Myeloid, Acute/genetics
Membrane Glycoproteins/ genetics
Nucleic Acid Hybridization
P-Glycoprotein
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics
RNA, Messenger/ analysis
RNA, Neoplasm/ analysis
Tumor Cells, Cultured},
   year = {1992}
}

@inproceedings{Diddens-1992,
   author = {Diddens, H.},
   title = {Role of multidrug resistance in photodynamic therapy},
   editor = {Thomas, J. Dougherty},
   publisher = {SPIE},
   volume = {1645},
   pages = {115-123},
year = { 1992},
url = { https://doi.org/10.1117/12.60934}

}

@article{Kimming,
   author = {Kimmig, A. and Gekeler, V. and Neumann, M. and Frese, G. and Handgretinger, R. and Kardos, G. and Diddens, H. and Niethammer, D.},
   title = {Susceptibility of multidrug-resistant human leukemia cell lines to human interleukin 2-activated killer cells},
   journal = {Cancer Res},
   volume = {50},
   number = {21},
   pages = {6793-9},
   note = {Using Smart Source Parsing
Nov 1},
   abstract = {Considering the possibility to overcome drug resistance by other treatment strategies than chemotherapy we investigated the susceptibility of three independently selected multidrug-resistant sublines of the T-lymphoblastoid leukemic cell line CCRF-CEM to lymphokine-activated killer (LAK) cells. We found that two of the multidrug-resistant sublines were significantly less susceptible targets to LAK cells. A third one, however, was as susceptible as the parental CCRF-CEM cell line. Moreover, a multidrug-resistant subline that reverted to an almost drug-sensitive phenotype was observed to be also revertant for resistance against LAK cells. We found an inverse relationship between the expression of the mdr1 gene (P-glycoprotein) and the susceptibility to LAK cells. Verapamil, a calcium channel blocker, while increasing the drug sensitivity of a multidrug-resistant subline, did not induce a reversal of the suppression of LAK susceptibility. The possibility of enhanced resistance to LAK cells of multidrug-resistant cells should be taken into account when one is looking for therapy strategies to overcome multidrug resistance.},
   year = {1990}
}

@article{Bahnmüller,
   author = {Bahnmüller, U. and Keller-Schierlein, W. and Brandl, M. and Zähner, H. and Diddens, H.},
   title = {Metabolites of Microorganisms},
   journal = {J. Antibiot.},
   volume = {1988},
   number = {1552 - 1560},
   pages = {8},
   note = {Journal Article
},
   year = {1988}
}

@article{Diddens,
   author = {Diddens, H. and Niethammer, D. and Jackson, R. C.},
   title = {Patterns of cross-resistance to the antifolate drugs trimetrexate, metoprine, homofolate, and CB3717 in human lymphoma and osteosarcoma cells resistant to methotrexate},
   journal = {Cancer Res},
   volume = {43},
   number = {11},
   pages = {5286-92},
   note = {Diddens, H
Niethammer, D
Jackson, R C
CA 18129/CA/NCI NIH HHS/
Cancer Res. 1983 Nov;43(11):5286-92.},
   abstract = {Methotrexate (MTX)-resistant sublines of malignant human cells were selected in vitro by stepwise increase in drug concentration in the medium. By this procedure a subline of Burkitt's lymphoma cells (RAJI) was made 290-fold resistant (RAJI/MTX-R), T-cell leukemia cells (CCRF-CEM) were obtained 210-fold resistant (CEM/MTX-R), and 3 MTX-resistant human osteosarcoma lines were selected: TE-85/MTX-R (19-fold resistant; relative to wild-type); MG-63/MTX-R (8-fold resistant); and SAOS-2/MTX-R (200-fold resistant). We also studied a B-cell lymphoblastoid line, WI-L2/m4, that was 13,000-fold resistant. Assay of cellular dihydrofolate reductase (DHFR) showed the following pattern of activity in resistant cell lines, relative to parental cell activity: RAJI/MTX-R, 550-fold increased; CEM/MTX-R, unchanged; TE-85/MTX-R, 4-fold increased; MG-63/MTX-R, 6-fold increased; SAOS-2/MTX-R, unchanged; and WI-L2/m4, 110-fold increased. Measurement of MTX membrane transport showed decreased uptake in CEM/MTX-R and SAOS-2/MTX-R, relative to parental cell lines. The other DHFR-overproducing cells all gave normal initial MTX uptake rates but increased total uptake. The DHFR-overproducing lines all had significant cross-resistance to both metoprine and trimetrexate; the two lines with defective MTX transport were not cross-resistant, and the CEM/MTX-R cells showed collateral sensitivity to these agents. Only minor cross-resistance to homofolic acid was found in all MTX-resistant lines. The highly MTX-resistant RAJI/MTX-R and WI-L2/m4 cells showed minor cross-resistance to the dual inhibitor of thymidylate synthetase and DHFR, CB3717 (5- and 15-fold, respectively). These studies demonstrated that, depending upon the mechanism of resistance, MTX-resistant human tumor cells may be effectively killed by antifolates with different routes of uptake into cells, or with a different enzyme target. Thus, there are at least three functionally distinct classes of folate antagonist with antitumor activity.},
   keywords = {Antineoplastic Agents/*toxicity
Biological Transport
Burkitt Lymphoma/drug therapy/metabolism
Cell Line
Drug Resistance
Folic Acid/analogs & derivatives/therapeutic use
Folic Acid Antagonists/*therapeutic use
Humans
Kinetics
Leukemia, Lymphoid/drug therapy/metabolism
Lymphoma/*drug therapy/metabolism
Methotrexate/metabolism/*therapeutic use
Osteosarcoma/drug therapy/metabolism
Pyrimethamine/*analogs & derivatives/therapeutic use/toxicity
Quinazolines/therapeutic use/toxicity
Structure-Activity Relationship
T-Lymphocytes/drug effects
Tetrahydrofolate Dehydrogenase/metabolism
Trimetrexate},
   year = {1983}
}

@article{Diddens,
   author = {Diddens, H. and Dorgerloh, M. and Zahner, H.},
   title = {Metabolic products of microorganisms. 176. On the transport of small peptide antibiotics in bacteria},
   journal = {J Antibiot (Tokyo)},
   volume = {32},
   number = {1},
   pages = {87-90},
   note = {Diddens, H
Dorgerloh, M
Zahner, H
JAPAN
J Antibiot (Tokyo). 1979 Jan;32(1):87-90.},
   keywords = {Anti-Bacterial Agents/*metabolism
Biological Transport
Escherichia coli/*metabolism
Immunodiffusion
Microbial Sensitivity Tests
Mutation
Peptides/*metabolism},
   year = {1979}
}

@article{Diddens1976,
   title        = {On the transport of tripeptide antibiotics in bacteria},
   author       = {Diddens, H. and Zähner, H. and Kraas, E. and Gohring, W. and Jung, G.},
   year         = 1976,
   journal      = {Eur J Biochem},
   volume       = 66,
   number       = 1,
   pages        = {11--23},
   note         = {Diddens, H Zahner, H Kraas, E Gohring, W Jung, G GERMANY, WEST Eur J Biochem. 1976 Jun 15;66(1):11-23.},
   abstract     = {The two tripeptide antibiotics L-2-amino-4-methylphosphinobutyryl-alanyl-alanyl-alanine (L-phosphinothricyl-alanyl-alanine) and L-(N5-phosphono)methionine-S-sulfoximinyl-alanyl-alanine, both inhibitors of the glutamine synthetase, are transported into the cell of Escherichia coli K 12 via the oligopeptide transport system. The uptake by this system is proved first of all by cross-resistance with tri-L-ornithine using oligopeptide-transport-deficient mutants, and secondly by antagonism tests demonstrating competitive reversal of the action of the antibiotic by several peptides which have been shown to be transported via the oligopeptide transport system, e.g. tri-L-alanine, tetra-L-alanine, tri-L-lysine, tri-L-serine, tri-glycine, glycyl-glycyl-L-alanine and the synthetic tripeptide L-azadenyl-aminohexanoyl-alanyl-alanine. On the other hand, there is no effect on the action of the antibiotic in antagonism tests with compounds which use different transport systems, such as L-alanyl-alanine, L-lysyl-lysine, glutathione and the synthetic amino acid azaadenylaminohexanoic acid, i.e. 2-amino-6-(7-amino-3H-v-triazolo-[4,5-d]-pyrimidin-3-yl)hexanoic acid. Another inhibitor of the glutamine synthetase, L-methionine-S-dioxide (methioninesulfone) could be converted into a tripeptide form by linkage to L-alanyl-alanine analogously to the tripeptide antibiotics described above. Whereas the free L-methionine-S-dioxide seems to be transported via the methionine transport system, the tripeptide form is transported via the oligopeptide transport system. Thus, this glutamine synthetase inhibitor can be taken up by the cell via two different transport mechanisms. Our results indicate that this could provide a synergistic effect. The syntheses of the new tripeptides L-azaadenylaminohexanoyl-alanyl-alanine and L-methionine-S-dioxidyl-alanyl-alanine were performed by dicyclohexylcarbodiimide couplings of the unusual N-protected L-alpha-amino acids azaadenylaminohexanoic acid and L-methionine-S-dioxide to L-alanyl-alanine-tert-butyl ester followed by common deprotection steps. Tri-L-ornithine was synthesized without carboxyl protection via two successive couplings of hydroxybenzotriazol esters of Nalpha-butoxycarbonyl-Ndelta-benzyloxycarbonyl-L-ornithine.},
   keywords     = {Anti-Bacterial Agents/*metabolism/pharmacology Biological Transport Cell Survival/drug effects Diffusion Escherichia coli/drug effects/*metabolism Fourier Analysis Glutamate-Ammonia Ligase/antagonists & inhibitors Magnetic Resonance Spectroscopy Oligopeptides/chemical synthesis/*metabolism/pharmacology Protein Conformation Structure-Activity Relationship}
}