Design, Synthesis and Conformational Studies of New Analogues of Temporins A and L

摘要

Temporins are short, linear 10-14 residues long peptides, with a net charge positive and an amidate C-terminal. To get insight into mechanism of action and biological activity of these compounds, we have investigated two members: temporin L (TL) (FVQWFSKFLGRIL-NH2) and temporin A (TA) (FLPLIGRVLSGIL-NH2). The first has the highest activity among all temporins but shows haemolytic activity too. TA active against Gram-positive bacterial strains, exerts the antimicrobial activity by its ability to form a transmembrane pore via a 'barrel-stave' mechanism or to form a 'carpet' on the membrane surface via the 'carpet-like' model [1,2]. We have investigated the preferential conformation of TL and TA in SDS and DPC solutions. On the bases of the NMR results, we have designed and synthesized new TA and TL analogues, called Pro~3TL (FVPWFSKFLGRIL-NH2), Gln~3TA (FLQLIGRVLSGIL-NH2), D-isomers (fvqwfskflgril-NH2) and a Retro-TL (lirglfksfwqvf-NH2) analogue.