Structural Response of Pohlianin C to Heterocyclic Graft Incorporation

In this paper, we investigate structural changes that occur upon the installation of oxazole and triazole heterocyclic amino acids (HAAs) into the cyclic octapeptide framework of Pohlianin C. Upon the introduction of the oxazole motif, the structural reorganization revealed an intramolecular hydrogen bond (IMHB) network that was more extensive than the one reported for the native peptide. Installation of the triazole was subsequently examined in a different area of the macrocycle. In this case, the structural changes in the backbone were more localized. Despite this, a notable change in the IMHB network took place compared to when only the oxazole had been introduced. Most interestingly, we found that the portion of the backbone adjacent to the oxazole was structurally conserved across both derivatives. Lastly, we examined the differences between the synthesized derivatives using HPLC retention times and found a link between the nature of HAAs and their lipophilicity.