Title:Therapeutic Peptides: Unravelling Conformational Dynamics by Systematic Application of Biophysical Techniques
Volume: 23
Issue: 9
Author(s): Nikita Pise, Arati Prabhu*, Radhika Raheja and Illham Dhala
Affiliation:
- Department of Pharmaceutical Chemistry & Quality Assurance, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy,
Mumbai, India
Keywords:
Therapeutic peptides, aggregation, conformation, dynamics, multidimensional NMR, peptide formulations.
Abstract: Peptide therapeutics represents one of the fastest-growing sectors in the pharmaceutical
drugs pipeline, with an increasing number of regulatory approvals every year. Their pharmacological
diversity, biocompatibility, high degree of potency and selectivity make them an attractive choice in
several therapeutic areas, such as diabetes, cancer, immune, metabolic, cardiovascular and infectious
diseases. However, the development of peptides as drugs presents its own set of challenges, necessitating
extensive property optimization aimed at improving their drug-like properties and stability in biological
environments. The discovery and development of innovative peptide therapeutic platforms entail
the employment of several biophysical techniques, which monitor the structural as well as the functional
integrity of peptides. Small structural changes of the bioactive peptides in response to the presence
of various excipients can have a major impact on their pharmaceutical prowess, necessitating the
use of analytical techniques for efficient quality control during development. Here we present some
widely used methods, such as circular dichroism, fluorescence spectroscopy and multi-dimensional
homo and heteronuclear nuclear magnetic resonance spectroscopy that form an integral part of therapeutic
peptides development. The application of combination biophysical platforms ensures the
maintenance of the appropriate folded structure, which is a prerequisite for the safety and efficacy of
peptide pharmaceuticals.