Effect of two simultaneous aza-β3-amino acid substitutions on recognition of peptide substrates by cAMP dependent protein kinase catalytic subunit

Selectivity Modulation and Structure of α/aza‐β3 Cyclic Antimicrobial Peptides

“…First, we developed strategies to synthesize large series of aza‐β 3 ‐amino acids bearing proteogenic or nonproteogenic side chains suitable for straightforward solid‐phase peptide synthesis . Then, we showed that peptides containing aza‐β 3 ‐amino acids can exert various biological activities and we synthesized highly stable AMP mimics with enhanced antimicrobial activities …”

“…The large variety of available side chains allowed us to design various aza‐β 3 ‐peptidomimetic sequences, while the abiotic moieties confer resistance against proteolytic degradation. Indeed, when incorporated into a linear peptide, aza‐β 3 ‐amino acids are known to enhance the resistance of the pseudopeptide to enzymatic degradation, and we showed that cyclic pseudopeptides combine high metabolic stability with a long half‐life . Significantly, the insertion of aza‐β 3 ‐amino acids in peptide sequences can also induce hydrazino turns in aqueous media, and we investigated the structure–activity relationship of linear antimicrobial aza‐β 3 peptidomimetics .…”

“…[42] First, we developeds trategies to synthesize large series of aza-b 3 -amino acids bearing proteogenic or nonproteogenic side chainss uitable for straightforwards olid-phase peptide synthesis. [43][44][45][46] Then, we showedt hat peptides containing azab 3 -amino acids can exert various biological activities [47][48][49] and we synthesized highly stable AMP mimics with enhanced antimicrobial activities. [50][51][52] The large variety of availables ide chains allowed us to design various aza-b 3 -peptidomimetic sequences, while the abiotic moieties confer resistance against proteolytic degradation.…”

“…Indeed,w hen incorporated into al inear peptide, aza-b 3amino acids are knownt oe nhance the resistance of the pseudopeptide to enzymatic degradation,a nd we showed that cyclic pseudopeptides combine high metabolic stability with a long half-life. [48,51] Significantly,t he insertion of aza-b 3 -amino acids in peptides equences can also induce hydrazinot urns in aqueous media, and we investigatedt he structure-activity relationship of linear antimicrobiala za-b 3 peptidomimetics. [50] While the mixed backbones can exhibit well-defineds tructures, the fact that the most active compounds are rather flexible feeds the ongoingd ebate whether stable conformations are advantageous or deleterious for antimicrobial activityi np eptidomimetic systems.…”