Synthesis and conformational studies of peptidomimetics containing a new bifunctional diketopiperazine scaffold acting as a beta-hairpin inducer.
A practical synthesis of a new bifunctional diketopiperazine (DKP) scaffold 1, formally derived from the cyclization of L-aspartic acid and (S)-2,3-diaminopropionic acid, is reported. DKP-1 bears a carboxylic acid and an amino functionalities in a cis relationship, which have been used to grow peptide sequences. Tetra-, penta-, and hexapeptidomimetic sequences were prepared by solution-phase peptide synthesis (Boc strategy). Conformational analysis of these derivatives was carried out by a combination of 1H NMR spectroscopy, IR spectroscopy, CD spectroscopy, and computer modeling, and reveals the formation of beta-hairpin mimics involving 10-membered and 18-membered H-bonded rings and a reverse turn of the growing peptide chain.
Ressurreição
Ana Sofia M
AS
Dipartimento di Scienze Chimiche e Ambientali, Università degli Studi dell'Insubria, Via Valleggio 11, I-22100 Como, Italy.
Bordessa
Andrea
A
Civera
Monica
M
Belvisi
Laura
L
Gennari
Cesare
C
Piarulli
Umberto
U
D032701:Biomimetics / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003500:Cyclization; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D012015:Reference Standards; D013237:Stereoisomerism
D054659:Diketopiperazines; D010455:Peptides