title: Construction of a polyproline structure with hydrophobic exterior using octahydroindole-2-carboxylic acid.
abstract: The proline analogue (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (Oic) has been previously applied as a proline substitute in pharmocologically active peptides and as a structural component of the antihypertensive drug Perindopril. Herein, we describe the formation of an oligoproline structure by an Oic oligomer. A series of Oic oligomers were investigated to show the structural and energetic contribution of appended residues to the structure. NMR investigation of these oligomers revealed an all-trans amide bond structure, and we provide evidence that a cascade-like mechanism is responsible for the all-trans folding cooperativity. X-ray crystallography of the Oic-hexapeptide clearly demonstrates that the all-trans structure of the Oic oligomer is a polyproline II helix. Thus, as a hydrophobic proline analog with a highly stable trans-amide bond, Oic represents an ideal building block for hydrophobic sites of polyproline II structures in biologically relevant contexts.
authors.affiliation: Biocatalysis group, Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str., 10, 10623, Berlin, Germany. kubyshkin@win.tu-berlin.de nediljko.budisa@tu-berlin.de.
authors.forename: Vladimir
authors.identifier: http://orcid.org/0000-0002-4467-4205
authors.initials: V
authors.lastname: Kubyshkin
authors.affiliation: Biocatalysis group, Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str., 10, 10623, Berlin, Germany. kubyshkin@win.tu-berlin.de nediljko.budisa@tu-berlin.de.
authors.forename: Nediljko
authors.initials: N
authors.lastname: Budisa
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D002264:Carboxylic Acids; D007211:Indoles; D010455:Peptides; C543265:octahydroindole-2-carboxylic acid; C011083:polyproline