Theoretical conformational analysis and synthesis of analogues of the heptapeptide antibiotic K-582 A.
A detailed theoretical conformational analysis of the linear heptapeptide antibiotic [Arg2]K-582 A (Arg-Arg-D-Orn-Thr-D-Orn-Lys-D-Tyr) was carried out. The results of the computer simulation suggest that the linear peptide has a high propensity to fold in solution into a quasi-cyclic conformation in equilibrium with pi(L-D) helices. The synthesis of two inactive analogues with an L-Lys in place of D-Orn3 or D-Orn5 confirms the importance of the proposed folding pattern for the occurrence of the antimicrobial activity of K-582 A.
De Coen
J L
JL
Free University of Brussels, Belgium.
Wathelet
B
B
Demeuse
F
F
Mayon
C
C
Culot
M
M
Brakel
J
J
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects; D003198:Computer Simulation; D005658:Fungi / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D011487:Protein Conformation; D017510:Protein Folding; D012996:Solutions; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D012996:Solutions; C086437:K 582 A