engleski

Anion binding by linear penta–homopeptides comprised of amino acids with nonpolar side chains

During the last few decades there has been a growing interest for developing linear and cyclic peptides for molecular recognition. Due to the fact that these compounds can mimic biomacromolecules as ion receptors, peptides can be used in medicine and pharmacology for drug discovery. It is well known that cyclic peptides generally exhibit improved metabolic stability and bioavailability, as well as enhanced binding affinity and selectivity toward different substrates compared to their more-flexible linear analogues. The main step in synthesis of such cyclic receptors is cyclization reaction which is often conducted in presence of templating agents. The main factor that affects its success is the conformational preorganization, that is the ability of a linear precursor to bring its reactive termini in the close spatial proximity. We have recently reported that, in addition to metal cations, the chloride anion is also able to act as directing agent for promoting the cyclization of linear peptides. In the scope of this work, we investigated the affinity of two linear homo- peptides L1 and L2, composed of nonpolar amino acids, namely L–leucine and L- isoleucine, towards several anions in acetonitrile by means of 1H NMR spectroscopy and microcalorimetry. The obtained results indicated that the anions other that chloride can also serve as very efficient templating agents for the intramolecular head-to-tail linear peptide cyclization.

anion binding ; homopeptides ; MD simulation ; NMR ; thermodynamics

nije evidentirano