Peptidsynthesen über N‐Phosphorylaminosäure‐phosphorsäure‐anhydride

N‐Dibenzylphosphoryl (DBP)‐aminosäuren (II) werden unter der Einwirkung von Diphenylphosphoryl(DPP)‐chlorid in gemischte Anthydride III übergeführt und diese mit Aminosäure‐benzylestern gekuppelt. Die erhaltenen N‐DBP‐Dipeptid‐ester IV werden durch katalytische Hydrierung oder durch Bromwasserstoff sämtlicher Benzylgruppen entledigt und unmittelbar in die freien Peptide VI übergeführt, da die intermediär sich bildenden N‐Phosphoryl‐peptide V infolge der herrschenden sauren Reaktion sofort entphosphoryliert werden. — Carbobenzoxy‐ bzw. Trityl‐aminosäuren lassen sich ebenfalls mit DPP‐Chlorid in gemischte Anhydride überführen und somit auch auf diese Weise mit anderen Aminosäuren verbinden. Copyright © 1961 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinhei

Diphenylmethylester der Phosphorsäure

The diphenylmethyl group has been found to be suitable for the protection of phosphoric or pyrophosphoric acid in condensation reactions. © 1965 Birkhäuser Verlag

On Cysteine and Cystine Peptides. III. Synthesis of a Fragment of Insulin Containing the Intrachain Disulfide Bridge

The application of methods developed mostly in this laboratory permitted the synthesis of the fully S,N-protected heptapeptides N-carbobenzoxy-S-trityl-l-cys-teinyl- S-diphenylmethyl - L- cysteinyl-L - alanylglycyl -L-valyl-S-trityl-L-cysteinyl-L-serine methyl ester (VIII, Figure 2), N-t-butyloxycarbonyl-S-trityl-L-cysteinyl-S-diphenylmethyl-L- cysteinyl - L- alanylglycyl-L- valyl-S-trityl-L-cysteinyl-L-serine methyl ester (X, Figure 2), and N-o-nitrophenylsulfenyl-S-benzoyl-L-cysteinyl-S-trityl-L - cysteinyl - L - alanylglycyl -L- valyl -S-benzoyl -L-cysteinyl-L-serine methyl ester (XXII, Figure 3). For these syntheses, a variety of N- and S-protecting groups was used; this allowed selective removal of either the N-, or two of three S-protecting groups according to desired aims. Thus, selective removal of the two S-trityl groups from VIII and X and of the two S-benzoyl groups from XXII led to the formation of the corresponding dithiol compounds XXV, XXVI, and XXVII. By oxidation of these thiol compounds a disulfide bridge was established specifically between two of the three cysteine residues incorporated in the above three heptapeptides. The corresponding oxidation products XXVIII, XXIX, and XXX are derivatives of the 6-12 sequence of the A chain of sheep insulin bearing the 6-11 intrachain bridge (Figure 1). Removal of the N-protecting groups from the cyclic peptide esters XXIX and XXX afforded the cyclic peptide ester hydrochlorides XXXI and XXXII from which the remaining S-protecting group can be removed by established methods. The significance of the above cyclic peptides as regards the problem of insulin synthesis is discussed. The possibility of an S→N acyl migration should be taken into account when using S-acylcysteines in peptide synthesis. It was proved that such a migration does not take place, at least in detectable extent, during the course of the synthesis of the S,N-protected heptapeptide XXII. © 1965, American Chemical Society. All rights reserved

Ten year treatment outcomes of radical prostatectomy vs external beam radiation therapy vs. brachytherapy for 1,503 patients with intermediate risk prostate cancer.

47 Background: To compare 10-year treatment outcomes of RP (radical prostatectomy) vs EBRT (external beam radiation therapy) vs BT (brachytherapy) for patients with IRPC (intermediate risk prostate cancer). Methods: A retrospective analysis using propensity score matching was performed on 1,503 IRPC patients who underwent treatment from 2004 to 2007. 819 underwent RP, 574 underwent EBRT to a median dose of 75.3 Gray, and 110 underwent BT using iodine-125. Biochemical failure was defined by the AUA (American Urological Association) definition of PSA (prostate specific antigen) failure for RP patients, and the ASTRO-Phoenix definition (American Society of Therapeutic Radiology and Oncology) for the EBRT and BT patients. Results: Median follow up was 10 years for RP, 9.6 for EBRT, and 9.8 for BT (range 1-13.4 years). With RP 76.3% had Gleason score 7 vs 72.8% for EBRT vs 57.3% for BT, p = 0.0001. Median initial PSA was 7.4 for RP, 9.4 for EBRT, and 8.3 for BT, p &lt; 0.0001. Neoadjuvant androgen deprivation therapy was given in 58.9% of EBRT patients vs 12.7% of BT vs 0.6% for RP, p &lt; 0.0001. Only 14% of BT received supplemental external radiation. The 10-year FFBF (freedom from biochemical failure) was 82.0% for BT vs 58.0% for RP vs 58.8% for EBRT, p &lt; 0.0001. Subset analysis of unfavorable IRPC patients showed a 10 year FFBF of 81.6% for BT vs 55.8% for RP vs 51.0% for EBRT, p &lt; 0.0001. The 10-year freedom from salvage therapy was 89.5% for BT vs 64.0% for RP vs 73.4% for EBRT, p &lt; 0.0001. There were no significant differences in distant metastases-free survival, prostate cancer-specific survival, or overall survival after adjusting for age. Multivariate analysis between pairwise groups with BT balanced by stabilized inverse probability of treatment weights showed that BT remained an independent predictor for improved FFBF, p = 0.049 for BT vs EBRT, and p &lt; 0.0001 for BT vs RP. Conclusions: Brachytherapy using iodine-125 is a reasonable treatment option for IRPC patients. Although BT showed improved FFBF after propensity score matching, this did not impact overall survival. </jats:p