Capping Motifs in Peptide-based Drugs and Peptidomimetics

Numerous motifs have been used to improve a particular function or extend the biological properties and structural profiles in peptides and peptidomimetics. For instance, amino-terminal Cu(II) and Ni(II), and pentapeptide motifs have been inserted into linear α-helical peptide sequences to generate metallodrugs and therapeutic peptides with dual antibacterial and immunomodulatory potential. Among the amino acid motifs found in peptides and proteins are those with capping effects at the N-terminus (N-cap) or C-terminus (C-cap) for α-helix and β-sheet stabilization. The primary aspect of peptide and peptidomimetics capping includes countering the helix macrodipole, providing additional hydrogen bonding interactions for structural stabilization, and generating unusual structural scaffolds with promising biological potential. In this context, the identification and engineering of motifs with possible capping effects is of great interest in the design of biologically active peptides and peptidomimetics, aiming to further explore this structural diversity to develop new peptide therapeutics.

The main goal of this Research Topic is to describe how different chemical modifications through the addition of capping motifs (e.g., amino acid capping motifs and N-acetyl-capping motifs) would lead to peptide-based drugs and peptidomimetics with diverse structural scaffolds and with improved translational potential to the clinic. Therefore, this Research Topic highlights the importance of N-capping and C-capping motifs in the development of structured peptides and peptidomimetics analogs with improved biological activities and high stability to numerous external agents, including temperature, pH and salt concentration variation, as well as proteolytic resistance. Thus, this Research Topic will appeal to a broad audience in fields such as peptide science, structure-function relationship, capping motifs, molecular biophysics, and medicinal chemistry.

We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Peptide-based drugs and peptidomimetics containing capping motifs
• Structural scaffolds diversity enabled by N-capping and C-capping motifs
• Structure-function correlation in peptides and peptidomimetics with capping motifs
• How capping motifs improve therapeutic potential in peptides and peptidomimetics
• Comparison of capping motifs for specific chemical and biological profiles
• Peptides and peptidomimetics containing capping motifs and their molecular targets

Keywords: N-capping motifs, C-capping motifs, Peptides, Peptidomimetics

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.