Synthetic Peptides as Molecular Probes in Biochemical Research: Design, Optimization, and Emerging Applications

Abstract

Synthetic peptides have emerged as versatile molecular probes in biochemical research, offering high specificity, tunability, and adaptability for applications in diagnostics, therapeutics, and fundamental biology. This review explores the design, synthesis, and optimization of synthetic peptides, emphasizing techniques such as Solid-Phase Peptide Synthesis (SPPS), orthogonal protection strategies, and chemical modifications including non-proteinogenic amino acid incorporation, cyclization, and hydrocarbon stapling to enhance stability, permeability, and functionality. Key applications are discussed, including probes for protein-protein interactions (PPIs), post-translational modifications (PTMs), enzyme kinetics, and molecular imaging modalities like fluorescence, PET/SPECT, and multimodal systems. Comparative analyses highlight peptides' advantages over small molecules and antibodies, while addressing biopharmaceutical challenges such as metabolic instability and immunogenicity. Future directions underscore the integration of artificial intelligence (AI) and computational tools for accelerated discovery. Overall, synthetic peptides bridge chemical biology and clinical translation, paving the way for personalized medicine and targeted therapies.