Theoretical conformational analysis and synthesis of analogues of the heptapeptide antibiotic K-582 A

Int J Pept Protein Res. 1994 Jan;43(1):10-8. doi: 10.1111/j.1399-3011.1994.tb00369.x.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides
  • Bacteria / drug effects
  • Computer Simulation*
  • Fungi / drug effects
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptides*
  • Protein Conformation
  • Protein Folding
  • Solutions
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Peptides
  • Solutions
  • K 582 A