Comparative physicochemical study of SIKVAV peptide and its retro and retro-enantio analogues

SIKVAV is an active site of laminin involved in different physiological and pathological functions, including neurite outgrowth, angiogenesis and tumor development. In this paper, we report the synthesis of the retro (reverse l-amino acid order) and retro-enantio (reverse d-amino acid order) analogues of the SIKVAV peptide, in order to compare their physicochemical characteristics. When a linear peptide is synthesized with d-amino acids (enantio modification) assembled in the reverse order (retro modification), it presents side chains orientation very similar to that in the original structure. Such peptidomimetic approach provides peptides with a higher metabolic stability. However, there is no evidence if this peptidomimetic approach also maintains the physicochemical characteristics of the original sequence. Surface activity, compression isotherms, kinetic penetration into l-α-Dipalmitoylphosphatidylcholine and l-α-phosphatidylcholine monolayers and miscibility with l-α-Dipalmitoyl-phosphatidylcholine at different molar ratios were determined for each peptide. Results show that either retro or retro-enantio modifications enhance the hydrophilic character of the SIKVAV sequence.