Peptides and Proteins as Drugs

Therapeutic peptides and proteins have gained significance as possible future drugs over the last three decades.

Recent advances in large-scale fermentation and purification procedures, as well as analytical characterisation, have broadened the boundaries.

Autoimmune illnesses, cancer, psychiatric disorders, hypertension, and some cardiovascular and metabolic diseases are among the conditions that may be treated with this sort of therapy. Protein drugs must be highly purified and concentrated, with a very short half-life and a storage stability of at least two years.

Recombinant technology has enabled the synthesis of numerous possible protein therapeutics at a reasonable cost, enabling for the treatment of serious, chronic, and sometimes fatal diseases such as diabetes, rheumatoid arthritis, hepatitis, and others.

Over 160 protein medicines are now available on the global market, with hundreds more in clinical testing.

The overall protein medicine industry is now worth more than $30 billion and is predicted to grow at least 10% each year.

One of the most promising areas for growth in the Protein Therapeutics Industry will be biogenerics, which is predicted to generate a multibillion market in the future.

Brief about Peptides and Proteins 

Over 7000 naturally occurring peptides have been found, and many of them have important functions in human physiology, such as acting as hormones, neurotransmitters, growth factors, ion channel ligands, or anti-infectives 1, 2, 3, 4. Peptides, in general, are highly selective and effective signalling molecules that bind to specific cell surface receptors, including such G protein-coupled receptors (GPCRs) or ion channels, wherein they activate intracellular effects. Peptides are a good starting point for the creation of new treatments due to their appealing pharmacological profiles and intrinsic features, and their specificity has been shown to translate into outstanding safety, tolerability, and effectiveness profiles in humans.

This feature may also be the key distinguishing feature of peptides as compared to typical small molecules. Furthermore, peptide therapies are frequently linked with lesser manufacturing complexity as compared to protein-based biopharmaceuticals, and as a result, production costs are lower, nearing those of small molecules.

Peptides are thus, in many respects, at the crossroads of small molecules and biopharmaceuticals. Natural peptides are frequently unsuitable used as convenient treatments due to inherent flaws such as low chemical and physical stability as well as a small circulating plasma half-life. These issues must be solved before they may be used as medications.

Some of these flaws have been effectively addressed through what we call “conventional design” of therapeutic peptides, as explained below.

Aside from classical peptide design, a variety of peptide technologies that offer prospects and future directions in the peptide industry are emerging.

Multifunctional and cell penetrating peptides, and also peptide drug conjugates and technologies concentrating on alternate routes of administration, are examples of these.

We propose a series of ideas that lead to the completion of peptides that have immense promise as future treatments.

Protein and peptides structure

• Proteins are huge molecules that are made up of one or even more amino acids in a precise order

• Proteins and peptides adopt three-dimensional conformations, and protein structure is closely connected to function

• This means that if the structure or form of a protein is affected, the function will be altered as well

• Protein structures are classified into four types (a) fundamental structure (b) secondary structure (c) tertiary structure (d) quaternary structure

• A target peptide is a short peptide chain of amino acids (typically 3-70) that guides protein and peptide transport to specific cell regions such as the mitochondria, nucleus, endoplasmic reticulum (ER), apoplast, chloroplast, peroxisome, and plasma membrane

• After the proteins were delivered, the signal peptidase enzyme cut the target peptide

• The amino acids that are linked together by an amide linkage15 are known as peptide bonds

The Advantages of Peptides and Proteins as Drugs

Peptides and proteins offer enormous medicinal potential.

An industry for peptide and protein therapeutics is now projected to be worth more than $40 billion per year, accounting for 10% of the pharmaceutical market.

This market is expanding significantly faster than the market for small molecules and will account for an even higher market share in the future.

The Disadvantages of Peptides and Proteins as Drugs

These peptide and protein therapies are not without drawbacks, including limited bioavailability and metabolic liability. Peptide oral bioavailability is restricted by GI tract breakdown and also their inability to pass the epithelial barrier. These medicines have high MWs, poor lipophilicity, and charged functional groups, which make them difficult to absorb. 

Because of these properties, most orally given peptides have a poor bioavailability (2%), as well as short half-lives (30 min). 

Although intravenous (iv.) or subcutaneous (sc.) administration of these therapeutics overcomes the matter of absorption, other factors such as systemic proteases, rapid metabolism, opsonization, conformational changes, dissociation of subunit proteins, non-covalent complexation with blood products, and destruction of labile side-groups limit the bioavailability of peptide and protein therapeutics.

Conclusion

Proteins and peptides have crucial roles as regulators in biological processes in most situations, but not all. Their aberrant activity has been linked to the development of a variety of human illnesses, including cancer, diabetes, and neurodegenerative disorders 9-11.

In most situations, pharmaceutical carriers are utilised to boost medication stability, potency, and lessen unwanted side effects, as well as to aid intracellular drug delivery.