Who needs “normal” peptides?
If you ask anyone, “What is a peptide?”, you will probably get a stock answer involving a chain of 2 or more amino acids which link together via a “peptide” linkage (-C(O)-NH). You might learn there are 20 natural amino acids, and they are all in the same L- stereo configuration. You might also learn that they are great at getting the body to do stuff, but they don’t make great drugs because they have short half-lives. So, we need to modify natural peptides so that they behave more like drugs – we’ll find ways to make them more stable – but still have them doing all the nice things we like about them. We’ll cyclise them, stick fat on them, PEGylate them, conjugate them to make them better. This article looks at some of the ways peptides are modified, but also recognizes that unmodified peptides still have a role to play.
The interest in peptides as therapeutics have greatly increased over the last 10 years or so, though they are not everyone’s first choice as drugs. On the plus side peptides tend to have high specificity and affinity for the receptors they are targeting and have good toxicity profiles. On the other hand, they are easily metabolized and have short half-lives. Orally available peptides are extremely rare, and most are administered as depots or injectables.
Despite the practical disadvantages, peptides remain a very active area of interest with over 70 approved peptide therapeutics (1), and a predicted market of $25Bn in 2018 (2). In addition, there are reported to be over 600 peptides in various stages of preclinical and clinical development (2). Many of these peptide APIs rely on structural modifications to increase stability, but others, for example peptide vaccines, comprise only native peptide sequences.
A significant amount of research is ongoing to design modifications to peptides that impart favorable properties. In fact, as I write this article shortly ...