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Beyond Natural Limitations: Long‐Range Influence of Non‐Natural Flexible and Rigid β‐Turn Mimetics in a Native β‐Hairpin Motif
Author(s) -
Körling Matthias,
Geyer Armin
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500724
Subject(s) - chemistry , dipeptide , dihedral angle , turn (biochemistry) , stereochemistry , amino acid , bicyclic molecule , peptidomimetic , cyclic peptide , peptide , structural motif , molecule , organic chemistry , hydrogen bond , biochemistry
β‐Turns mediate diverse protein recognition processes, although dihedral angle preferences of canonical amino acids limit accessible β‐turn geometries. Organic synthesis can go beyond these limitations and either increase the mobility of a β‐turn or constrain it inside a bicyclic ring. Nine β‐turn dipeptides are studied here in the isolated β‐hairpin of the miniprotein Foldon, which is only moderately structured in the absence of the native protein environment. The dipeptide mimetics, which vary the backbone flexibility from linear alkyl chains to bicyclic dipeptides (Hot=Tap), are ranked against each other with regard to their hairpin‐stabilizing capacities. NMR‐derived parameters and melting temperatures correlate the backbone rigidity of the β‐turns with the hairpin population. In contrast to the general expectation, highly populated hairpins are not only observed for rigid dipeptides, but also for selected flexible amino acids in the i + 1 and i + 2 positions of the β‐turn.