What are peptides and their role in the body?

Understanding Peptides: Structure, Function, and Clinical Applications

Basic Definition and Structure

Peptides are short chains of amino acids linked together by peptide bonds, typically consisting of 2-50 amino acids, distinguishing them from larger proteins which contain more than 50 amino acids. 1

• Oligopeptides contain fewer than 10-20 amino acids, while polypeptides consist of more than 20 amino acids 1
• The peptide bond forms between the carboxyl group of one amino acid and the amino group of another, creating the backbone structure 2
• Peptides serve as the fundamental building blocks of proteins and carry essential molecular information for biological processes 3

Physiological Roles in the Body

Signaling and Communication Functions

• Peptides function as critical signaling molecules throughout all domains of life, acting as transmitters from the brain to the body to direct muscles and nerves to perform specific functions 4
• They serve as structural components of hormones, enzymes, toxins, and antibiotics, playing fundamental physiological roles 1
• Peptides interfere with protein-protein interactions, which are indispensable in biological processes 3

Specific Peptide Systems

Natriuretic peptides (including BNP and NT-proBNP) represent a clinically important peptide family that regulates cardiovascular homeostasis:

• These peptides are secreted by cardiac myocytes in response to mechanical stretch and volume overload 2
• They promote natriuresis, diuresis, and vasodilation while antagonizing the renin-angiotensin-aldosterone and sympathetic nervous systems 2
• Natriuretic peptides exert anti-proliferative and cytoprotective effects on myocardial and vascular structure, providing inhibition of cardiac and vascular remodeling 5
• They activate natriuretic peptide receptor-A (NPR-A), generating cyclic guanosine monophosphate to mediate their cardiovascular effects 5

Therapeutic Applications

Current Clinical Use

Since the introduction of insulin as the first commercial peptide drug, over 80 peptide-based drugs have reached the market for conditions including diabetes, cardiovascular diseases, and urological disorders. 1

• Peptides are ideally suited to mimic natural ligands and function in antagonistic or agonistic ways 6
• Their small size and specific binding properties allow them to physiologically disrupt functional protein complexes 6
• Peptides can address both extracellular targets (like cell surface receptors) and intracellular targets when coupled with appropriate delivery systems 6

Mechanisms of Therapeutic Action

• Peptides can cross membranes and reach intracellular targets, achieving numerous biomedical tasks that can hardly be mimicked by other chemical substances 3
• Many protein-protein interactions are mediated by "hot-spots" comprising only a small part of the binding interface but accounting for 80% of binding energy, providing targets for peptide-based pharmaceutical interventions 6
• Peptides can be optimized for binding affinity and stabilized through introduction of non-natural amino acids to form peptidomimetics resistant to cellular proteases 6

Emerging Applications

• Peptides have gained significant attention in the cosmetic industry for their potential in boosting skin health, beyond their traditional therapeutic roles 1
• Advanced nano-supramolecular technologies, aptamers, and modern smart bio-functional materials are expanding peptide applications in vaccines and drug/gene-targeted delivery systems 3
• Neutral endopeptidase inhibitors have been developed to prevent breakdown of endogenous natriuretic peptides, thereby enhancing their therapeutic effects 5

Important Clinical Considerations

Bioavailability and Stability Challenges

• Short hydrophilic peptides generally do not cross plasma membranes on their own, requiring coupling to carrier systems like liposomes or nanoparticles for intracellular delivery 6
• The physicochemical and proteolytic stability profiles determine the therapeutic potential of peptides 7
• Chemical modifications including cyclization, substitution with D-amino acids, N-methylation, and side-chain halogenation can enhance therapeutic profiles 7

Diagnostic vs. Therapeutic Paradox

• In heart failure, altered natriuretic peptide processing results in secretion of less biologically active forms (primarily proBNP rather than fully active BNP 1-32), which explains why administered BNP shows beneficial effects despite high concentrations of endogenous immunoreactive natriuretic peptides 5, 2
• This "natriuretic peptide paradox" highlights the distinction between using peptides as biomarkers versus therapeutic agents 5