When we learn biology at school, we are taught about the ”big three” biological molecules - carbohydrates, proteins and fats. But when I started looking closer at proteins, especially peptides, I realised something surprising. Some of the smallest molecules in this group are actually doing some of the biggest jobs in medicine.
So, what are peptides exactly?
I like to think of peptides as mini versions of proteins. They are made from amino acids (the same building blocks as proteins) but have much shorter sequences, typically between 2 and 50 amino acids. Despite being very small molecules, they have very important roles in our bodies. Some peptides help our cells react to signals and facilitate brain cell communication, while others, like insulin, regulate blood sugar levels. Because of these functions, they have a wide range of medical uses, including the treatment of metabolic disorders, infectious diseases and managing chronic pain. In this article, I’ll explore how peptide drugs are useful for the pharmaceutical industry, as well as appreciate how natural peptides have opened avenues for the creation of newer peptide drugs.
What makes peptides such good medicines?
Peptides have several unique characteristics that make them highly effective as medication. Their specific amino acid sequence and small size allow them to bind to receptors on the cell surface membrane with high specificity and trigger responses within cells. This high specificity is important because there are fewer interactions with unwanted targets, resulting in fewer side effects. [1] This is very valuable when it comes to chronic disease management in patients as adverse immune responses need to be minimised. [2]
However, peptides also come with a few challenges. One major limitation of peptides is their difficulty crossing cell membranes. Only specific molecules can pass through cellular membranes. This restricts which peptides can move across the membrane.[1] As a result, the majority of approved peptide drugs target receptors on the outside of cells rather than in them.
Another challenge is that peptides are easily broken down by enzymes in the digestive system. This means they are usually not formulated as tablets and given by injection instead. Unfortunately, this may lower patient compliance to take medication, particularly for chronic conditions which require patient-friendly regimens. [2]
Early peptide medicines
Early peptide medicines were natural hormones produced from living organisms such as pigs and cows. These natural peptides showed that peptide hormones could be isolated and used therapeutically even with their short half-lives.
People with type 1 diabetes rely on insulin because their bodies can’t produce it naturally. At first, insulin was extracted from animals. Early animal insulin caused adverse side effects as it contained a number of impurities. During the 1970s, purification of animal insulin helped to reduce these allergic reactions but nowadays, we can make human insulin using biotechnology. However, human hormones like insulin have a relatively short half-life, as they degrade quickly in the body. This means that people with type 1 diabetes need to take frequent injections, demonstrating the issue with the low stability of peptide hormones. To combat this, chemical modifications would need to be made to improve its stability.
The early challenges with insulin inspired innovations which transformed how we discover and develop newer peptide drugs. These newer peptide medications may be chemically modified or entirely made from scratch.
New peptide developments
Being able to isolate and study naturally occurring peptides has opened the doors for the development of modern peptide drugs. Natural peptides can be and have been modified for therapeutic use, producing peptide analogues. These are synthetic or modified versions of naturally occurring peptides that have a similar structure and function.
Ozempic: the weight loss drug
Semaglutide, which is commercially known as Ozempic, is an injectable anti-diabetic medication used to treat individuals with type 2 diabetes but can also be prescribed for weight loss. The development of semaglutide is based on a natural hormone called glucagon-like-peptide-1 (GLP-1). GLP-1 helps regulate blood sugar levels, something people with type 2 diabetes cannot do. Scientists modified this peptide so it has a longer-lasting effect in the body, making it more effective for treating diabetes. [1]
MK-0616: the cholesterol drug
Not all peptide drugs come from modifying natural molecules. Some are designed entirely from scratch using advanced scientific technology. An example of this is MK-0616. MK-0616 is an experimental, once-daily pill designed to lower "bad" (LDL) cholesterol.
To understand how this works, it is helpful to consider the “lock and key” model. In biology, some molecules produce a response or release a product if they fit together perfectly, just like a key fits into a specific lock. The lock in this case is the LDL receptor found on the surface of liver cells and the key is the molecule that binds to it. This is what scientists mean when we talk about specificity.
These receptors usually bind to LDL, which is then taken into the cell, where it is broken down. This process lowers the concentration of LDL in the bloodstream.
However, there is another protein called PCSK9 which can also bind to the LDL receptors. When this happens, the receptors are destroyed instead of being reused. Fewer receptors mean less “bad” cholesterol can be removed from the blood so LDL levels increases.[4,5] This is where MK-0616 acts. MK-0616 binds to PCSK9 and prevents it from binding to LDL receptors. Therefore, LDL can be removed from the blood, lowering cholesterol. Clinical trial data has demonstrated how effective the drug is, with studies reporting reductions in LDL cholesterol of up to 60% within just 8 weeks! [3]
Although there are already injectable treatments targeting PCSK9, they require repeated injections and can be difficult for some patients to access, which has led to adoption rates not meeting expectations. A daily pill like MK-0616 could make treatment much more accessible.
Ultimately, peptides are becoming more important in healthcare due to their clinical applications and their potential to treat specific conditions. The scientific advancement of peptides as medicines could change how we treat many conditions. What I find most exciting about peptides is that they are shaping the future of medicine as we are moving towards more personalised healthcare. From insulin first being extracted from dogs to Ozempic and experimental drugs like MK-0616, peptides have come a long way.
Tomini I. University Second Year
References
[1] Fetse, J., Kandel, S., Mamani, U.-F. and Cheng, K., 2023. Recent advances in the development of therapeutic peptides [Online]. Trends in Pharmacological Sciences, 44(7), pp.425–441. Available from: https://doi.org/10.1016/j.tips.2023.04.003 [Accessed 12 July 2026].
[2] Zheng, B., Wang, X., Guo, M. and Tzeng, C.-M., 2025. Therapeutic Peptides: Recent Advances in Discovery, Synthesis, and Clinical Translation [Online]. International Journal of Molecular Sciences, 26(11), pp.5131–5131. Available from: https://doi.org/10.3390/ijms26115131 [Accessed 12 July 2026].
[3] Oral PCSK9 Inhibitor Substantially Reduces Cholesterol in Phase 2 Trial - American College of Cardiology, 2023. American College of Cardiology [Online]. Available from: https://www.acc.org/About-ACC/Press-Releases/2023/03/06/14/02/Oral-PCSK9-Inhibitor-Substantially-Reduces-Cholesterol?utm_source=chatgpt.com [Accessed 12 July 2026].
[4] Page, M.M. and Watts, G.F., 2016. Experimental and clinical pharmacology: PCSK9 inhibitors - mechanisms of action [Online]. Australian Prescriber, 39(5), pp.164–167. Available from: https://doi.org/10.18773/austprescr.2016.060 [Accessed 12 July 2026].
[5] Binod Pokhrel, Pellegrini, M.V. and Levine, S.N., 2024. PCSK9 Inhibitors [Online]. Nih.gov. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448100/#:~:text=PCSK9%2C%20a%20product%20of%20hepatocytes,the%20clearance%20of%20LDL%2DC [Accessed 12 July 2026].
