What Are Peptide Drugs and How Are They Used in Therapeutics?
Peptide drugs, also known as therapeutic peptides, are short chains of amino acids, typically consisting of molecular weights of 500-5000 Da. These molecules are designed to mimic natural peptides that play crucial roles in biological processes, acting as hormones, neurotransmitters, growth factors, ion channel ligands, or anti-infective agents. Harnessing these functions, peptide drugs are developed to target specific pathways and diseases, offering unique therapeutic advantages over traditional small molecules or biologics.
Peptide therapeutics are highly versatile. They have demonstrated efficacy in treating diabetes, cancer, cardiovascular diseases, and infectious diseases.
Peptide Drug Discovery: From Concept to FDA Approval
The development of therapeutic peptides follows a multi-step path, that started with the discovery of natural peptides and their analogs. Early peptide drug discovery involved isolating hormones like insulin or somatostatin, whose physiological roles were well understood.
Over time, advances in proteomics and structural biology led to the discovery of many protein-protein interactions (PPIs), which are vital for cellular functions like signal transduction, immune response, and cell cycle regulation. Dysregulated PPIs lead to diseases such as cancer and autoimmune disorders.
Peptides, due to their structural flexibility, can bind effectively to the complex surfaces involved in these interactions, offering a targeted approach to disrupt pathological PPIs. The rational design of peptides for modulating PPIs leverages computational and experimental approaches to target specific molecular interfaces with high precision. Identification of the structural and functional properties of the protein interaction surface using advanced techniques such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy is the first step. Computational algorithms then help design peptides that bind selectively to these surfaces, mimicking natural interactions or inhibiting pathological ones.
Following discovery, peptide production is achieved through chemical or biological methods. Peptide synthesis techniques, such as solid-phase peptide synthesis (SPPS) and recombinant DNA technology, allow for the creation of modified peptides with improved stability and efficacy. SPPS remains a cornerstone for synthesizing short to medium-length peptides, while recombinant DNA technology is employed for longer or more complex structures. After synthesis, chemical modifications, such as PEGylation or cyclization, are applied to enhance bioavailability, stability, and half-life.
These optimized peptides undergo rigorous preclinical and clinical evaluations, ultimately leading to their inclusion in the growing FDA-approved peptide drug list.
Preclinical Development
In the preclinical stage, peptide drugs undergo extensive testing in vitro and in vivo, with animal models, to evaluate their safety, efficacy, and pharmacokinetics. This stage also focuses on refining the manufacturing process to ensure consistency and scalability.
Clinical Trials, FDA Approval, and Beyond
Clinical trials for peptide drugs are conducted in three phases:
- Phase I: Tests safety, dosage, and pharmacokinetics in a small group of healthy volunteers or patients.
- Phase II: Evaluates efficacy and further safety measures in a larger patient population.
- Phase III: Confirms efficacy, monitors adverse reactions, and compares the peptide drug to existing treatments in a much larger population.
After the successful completion of these trials, the drug developer submits a New Drug Application (NDA) to the competent regulatory agency. Upon approval, peptide drugs are added to the FDA-approved peptide drugs list, signaling their readiness for market distribution. Continuous post-marketing surveillance ensures long-term safety and efficacy.
Insulin, first synthesized in 1921, marked the beginning of therapeutic peptide development. A century later, there are over 80 peptide drugs approved by the Food and Drug Administration (FDA), spanning therapeutic areas such as urology, respiratory medicine, metabolic disorders, and cardiovascular conditions. The rapid growth of this field is evident from the 36 peptide drugs approved between 2015 and 2022, accounting for approximately 10% of all medications approved during that time. Currently, more than 170 peptides are undergoing active clinical development, with numerous others advancing through preclinical studies.
Glucagon-Like Peptide-1 Drugs: Advances in Diabetes Treatment
Glucagon-like peptide-1 drugs have revolutionized the management of type 2 diabetes. Peptide drugs for diabetes mimic the natural GLP-1 hormone, which stimulates insulin secretion, suppresses glucagon release, and slows gastric emptying. The combined effects help regulate blood sugar levels and reduce appetite.
These peptides are highly susceptible to enzymatic hydrolysis by digestive enzymes in the stomach and intestines, necessitating parenteral administration via injection. This challenge presents an opportunity to refine delivery systems and optimize alternative administration routes. One promising approach is co-formulation with permeation enhancers. Semaglutide co-formulated with sodium N-[8-(2-hydroxybenzoyl amino]caprylate (SNAC) decreases the efficacy of digestive enzymes, preventing gastric degradation. It has been approved for oral administration to treat type 2 diabetes.
Glucagon-like peptide-1 (GLP-1) drugs, which are GLP-1 receptor agonists, represent a significant advancement in the use of peptides for treating type 2 diabetes mellitus. Since the approval of Exenatide in 2005, the field has progressed notably, culminating in the development of Semaglutide, which received approval in 2017.
Beyond diabetes, research suggests potential applications in treating neurodegenerative disorders, such as Alzheimer’s disease, due to their anti-inflammatory and neuroprotective properties. Moreover, GLP-1 receptor agonists like semaglutide have shown potential in reducing cardiovascular risks in diabetic patients.
AMSbiopharma Peptide Analysis Ensures Reliability, Safety, and Compliance
Peptide drugs represent a critical advancement in modern medicine, offering targeted, effective, and safe treatments for multiple diseases. From GLP-1 drugs in diabetes to innovative peptide drugs for cancer, these therapeutics continue to transform patient care.
AMSbiopharma’s services play a crucial role in the preclinical development phase by offering advanced analysis of biopharmaceuticals. We provide in-depth peptide and protein analysis services, supporting the optimization of peptide-based pharmaceutical products for market success.
We can conduct peptide mapping, determination of intact protein molecular weight, and isoform analysis using Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UPLC-HRMS) and Ultra-Performance Liquid Chromatography-Diode Array Detector-High Resolution Mass Spectrometry (UPLC-DAD-HRMS). We also perform the detection and quantification of synthetic peptides using UPLC-Tandem Mass Spectrometry (MS/MS).
These techniques are essential for characterizing peptides and ensuring their safety and efficacy before moving to clinical trials.
At AMSbiopharma, we are committed to contributing to this evolving landscape and expanding the FDA-approved peptide drugs list, bringing new hope to patients worldwide. Our expertise in analyzing peptide-based pharmaceuticals ensures the reliability, safety, and compliance of these therapeutics throughout development and beyond.
References
- Del Olmo-Garcia MI, Merino-Torres JF. GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes. J Diabetes Res. 2018 Apr 2;2018:4020492. doi: 10.1155/2018/4020492
- Khadka S, Tabassum N, Khan FU, Shaukat F, Mukherjee S. Peptides and proteins: Natural sources, functions, and applications as therapeutics. Jundishapur J Nat Pharm Prod. 2022;17(4):e134049. doi:10.5812/jjnpp-134049.
- Solis-Herrera C, Kane MP, Triplitt C. Current Understanding of Sodium N-(8-[2-Hydroxylbenzoyl] Amino) Caprylate (SNAC) as an Absorption Enhancer: The Oral Semaglutide Experience. Clin Diabetes. 2024 Winter;42(1):74-86. doi: 10.2337/cd22-0118
- Wang L, Wang N, Zhang W, Cheng X, Yan Z, Shao G, Wang X, Wang R, Fu C. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022 Feb 14;7(1):48. doi: 10.1038/s41392-022-00904-4.
- Wang W, Wang Q, Qi X, Gurney M, Perry G, Volkow ND, Davis PB, Kaelber DC, Xu R. Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimers Dement. 2024 Dec;20(12):8661-8672. doi: 10.1002/alz.14313