Aza-Isotryptophan: Synthesis, Pictet-Spengler Chemistry, Incorporation and Conformational Analysis in Peptides, and Activity in Modulators of the Cluster of Differentiation-36 Receptor

Isotryptophan (Itr) is the rare 2-indoyl counterpart of the essential amino acid tryptophan. Considering potential to explore novel side chain -space in a residue prone to adopt backbone turn conformers, azaItr has been effectively synthesized and employed in Pictet-Spengler and peptide chemistry. -Turn geometry was characterized in model peptides of the Ala-azaItr-D-Phe triad by X-ray and NMR analyses. Moreover, azaItr analogs of growth hormone releasing peptide-6 (GHRP-6) demonstrated promising cluster of differentiation 36 receptor (CD36) binding affinity and modulatory effect on the inflammatory response induced by the activated complex composed of the latter co-receptor in the Toll-like receptor-2/6 heterodimer.