02282nas a2200241   4500008004100000022001400041245010000055210006900155260000800224300001100232490000800243520144900251653002001700653003801720653002501758653001701783653002001800100001601820700002001836700003601856700002601892856012201918       2024                        eng d  a0045-206800aMacrocyclic peptides derived from AcPHF6*and AcPHF6 to selectively modulate the Tau aggregation0 aMacrocyclic peptides derived from AcPHF6and AcPHF6 to selectivel  cOCT  a1076250 v1513 a<p>
	Ten macrocyclic peptides, each comprising 14 amino acids, were designed and synthesized based on the Tau aggregation model hexapeptides AcPHF6* and AcPHF6. The design took into account the aggregation tendencies of each residue in AcPHF6* and AcPHF6, their aggregation models, while employing peptide-based structural design principles including N-methylation to promote turns and to block hydrogen bond propagation and elongation of the aggregation chain. NMR analysis supported that all these peptides adopted an antiparallel beta-sheet conformation. Self-aggregation studies characterized the aggregation properties of these peptides, identifying two peptides with the highest (P3) and lowest (P8) aggregation tendencies. In cross-aggregation studies with the parent peptides AcPHF6* and AcPHF6, P3 and P8 were found to promote and reduce aggregation, respectively. Furthermore, P3 and P8 demonstrated an enhancement and diminution effect on the aggregation of K18wt, indicating their capacity to modulate aggregation even at the macromolecular level. Thus, the two simple peptides, P3 and P8 selectively exhibit pro- or anti-aggregation effects on PHF peptides and Tau. This study, has thus developed structurally well-defined non-complex peptides, derived from AcPHF6* and AcPHF6, to modulate Tau aggregation as desired, offering applications in Tau model studies and the development of Tau aggregation inhibitors or promoters.</p>
10aCyclic peptides10aPeptide -based drug design (PBDD)10aPeptide conformation10aPHF peptides10aTau Aggregation1 aDangi, Abha1 aQureshi, Tazeen1 aChinnathambi, Subashchandrabose1 aMarelli, Udaya, Kiran  uhttps://library.ncl.res.in/content/macrocyclic-peptides-derived-acphf6and-acphf6-selectively-modulate-tau-aggregation