Diaminodiacid‐Based Solid‐Phase Synthesis of Peptide Disulfide Bond Mimics

Abstract

Das antimikrobielle Peptid Tachyplesin I wurde als Modell für die Titelstrategie verwendet, die zur Herstellung von peptidischen Makrocyclen mit doppeltem Disulfidersatz entwickelt wurde. Die Faltung und Aktivität der Analogen von Tachyplesin I variierten abhängig von den Disulfidsurrogaten. SPPS=Festphasenpeptidsynthese.

Adrenomedullin disulfide bond mimetics uncover structural requirements for AM1 receptor activation

“…Diaminodicarboxylic acid (DADC) building blocks x , y , and z (Figure A) were synthesized according to literature and used for the synthesis of analogs 15 to 17 as described before . Exemplarily, the synthesis strategy for thioether analog 16 (u 16 , Cys 21 ) is shown in Figure D.…”

Synthesis and antibacterial activities of novel tyrocidine A glycosylated derivatives towards multidrug‐resistant pathogens

“…As shown in Scheme , the first Phe residue was anchored to 2‐chlorotrityl chloride resin with Fmoc‐Phe‐OH in the presence of DIPEA. Next, the glycopeptides were assembled via sequential introduction of Fmoc‐Pro‐OH, Fmoc‐ d ‐Phe‐OH, Fmoc‐Leu‐OH, Fmoc‐Orn(Boc)‐OH, Fmoc‐Val‐OH, Fmoc‐Tyr(tBu)‐OH, Fmoc‐Gln(Trt)‐OH, building blocks 3a–4f , and Fmoc‐ d ‐Phe‐OH using 20% piperidine as Fmoc‐removed reagents and HCTU(N,N,N',N'‐Tetramethyl‐O‐(6‐chloro‐1H‐benzotriazol‐1‐yl)uronium hexafluorophosphate)/DIPEA in coupling reactions . Subsequently, the loaded resins were treated with AcOH/TFE/dichloromethane (DCM) (1 : 1 : 8) to give the linear glycopeptides 9a–f and 10a–f .…”

A Diaminodiacid (DADA) Strategy for the Development of Disulfide Surrogate Peptides

“…[8] One possible alternative strategy is based on pre-made diaminodiacid building blocks, which incorporate the disulfide surrogate and are included in the assembly of the peptide through SPPS ( Figure 2). [9,10] In pioneering studies, the Vederas and van der Donk groups demonstrated the use of DADA strategy in synthesis of naturally occuring lantibiotics. [10] A series of DADA building blocks have also been developed and incorporated into various peptides.…”

“…[10] A series of DADA building blocks have also been developed and incorporated into various peptides. [9][10] This review summarizes the development of the DADA strategy for the synthesis of disulfide surrogate peptides. We describe the principle of the DADA strategy, the development of DADA building blocks, and the effect of DADA replacement on peptide structures and activities.…”