Synthetic turn mimetics and hairpin nucleators: Quo Vadimus?

Abstract

Structural mimicry of peptides has witnessed perceptible progress in the last three decades. Reverse turn and β-hairpin units are the smallest secondary structural motifs that are some of the most scrutinized functional cores of peptides and proteins. The practice of mimicking, without altering the function of the bioactive core, ranges from conformational locking of the basic skeleton to total replacement of structural architecture using synthetic analogues. Development of heterogeneous backbones--using unnatural residues in place of natural ones--has broadened further opportunities for efficient structural rigidification. This feature article endeavours to trail the path of progress achieved hitherto and envisage the possibilities that lie ahead in the development of synthetic turn mimetics and hairpin nucleators.

The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

“…1 As an essential components of β-hairpins (the fundamental elements of anti-parallel βsheets), the β-turns are considered as a nucleators or initiation sites that bring the two peptide strands in close proximity, enabling their interactions through hydrogen bonding. 7 On the basis of the previous results, 1,n-disubstituted ferrocenes are established as molecular templates for the design of turns and β-sheet-like structures as the almost free rotating cyclopentadiene (Cp) rings are separated by about 3.3 Å which is ideal for interstrand hydrogen bonding in their conjugates comprised of natural amino acids or peptides. 5 The small model compounds containing molecular templates capable of inducing β-sheet structures in attached peptide strands have been very useful in studies of β-sheet folding and interactions.…”

Modulating Hydrogen Bonded Self-assembled Patterns and Morphological Features by a Change in Side Chain of Third Amino Acid of Synthetic γ- Amino Acid Based Tripeptides

“…In proteins, turn nucleation is the characteristic function which results the peptide backbone to fold back into its initial position. α‐Amino acid based tripeptides and tetrapeptides adopt 7‐membered H‐bonded γ‐turn or 10‐membered H‐bonded β‐turn structures . These chain reversals are again classified into subtypes by consideration of dihedral angles and folding pattern .…”

“…α‐Amino acid based tripeptides and tetrapeptides adopt 7‐membered H‐bonded γ‐turn or 10‐membered H‐bonded β‐turn structures . These chain reversals are again classified into subtypes by consideration of dihedral angles and folding pattern . The turn type structural elements, made up with α‐peptides, can be mimicked with synthetic building blocks .…”

“…[2][3][4][5][6] These chain reversals are again classified into subtypes by consideration of dihedral angles and folding pattern. [2][3][4][5][6] The turn type structural elements, made up with a-peptides, can be mimicked with synthetic building blocks. [7][8][9] In bio-medicinal chemistry, peptidomimetic approaches are utilized to design small molecules, which have wide applications in molecular recognition, protein-protein interactions, protein inhibition and drug discovery.…”

Synthesis and DNA‐Binding Studies of A New Cyclic Dimeric Symmetrical Pseudo‐Turn Mimetic

“…The synthetic mimic is such designed that it may be capable of binding to the targeted area of interest and that will directly result into some biological response. Thus, efforts have been made to achieve synthetic analogues mimicking different turn like structure such as β‐turns, γ‐turns, α‐helices etc. Ample of reports are available in the literature where efforts were directed towards achieving cyclic turn mimetics .…”