Among the three general classes of compounds namely small molecules, antibodies and peptides, the group of molecules familiar to a pharmacologist as peptides holds very special significance. Peptides are short chains of upto 50 amino acids, which occur naturally or can be synthesized. The advantages of peptides in therapeutics are their high specificity and activity, low accumulation without causing problems associated with bio-magnification and toxicity, low immunogenic response, a chemically unique three dimensional characteristic and relative ease of chemical synthesis, upscaling to pilot plant and manufacture in bulk.
Peptides, the small chain polymers of amino acids exist naturally in plants, animal and human beings where they play very crucial and critical role in their metabolism.
Peptidomimetics as an interesting field of study actually originated with the unfolding of the astonishingly crucial role peptides play in human and animal metabolism. It is now very well established, after around four decades of study worldwide, that peptides are a class of compounds which exhibit significantly important activity prompting to investigate their role as antibiotics, hormones, platelet aggregate inhibitors, somatostatins and immunosupressants. There are however some concerns associated with peptides such as low oral bio-availability thus necessitating their administration as a drug through the parenteral route. They are also less stable once introduced as drug which in some cases considered as disadvantageous. Low solubility in body fluids and high costs of chemical synthesis are the other minus points associated with peptides which however have not prevented the search for peptides with pharmacological properties to tackle difficult to deal diseases associated with cardiovascular and central nervous system, hormonal disorders and infections caused by various pathogenic organisms.
In India, peptide research purely as an academic field of study was perhaps initiated in the laboratory of the then Central College, University of Mysore, more than four decades ago. Among the few companies involved in peptide research and development, the Jupiter Group and its subsidiary Sven Genetech, has invested substantially over the past two and a half decades on peptide research and technology development particularly in the area of peptides as drug intermediates and active pharmaceutical ingredients. The company has since entered into the area of formulations using peptides as key ingredients to manufacture drugs, nutraceuticals and cosmoceuticals.
Peptide synthesis
Research on peptide synthesis is a widely investigated area of study in several institutions across the country, the leading institutions being Indian Institute of Chemical Technology, Hyderabad,
Department of Studies in Chemistry, Central College, Bangalore University, National Institute of Pharmaceutical Education and Research, Punjab, National Chemical Laboratory, Pune. Institute of Microbial Technology, Chandigarh, Institute of Nuclear Medicine and Allied Sciences, New Delhi, Indian Institute of Technology, Rourkee Department of Chemistry, University of Kalyani.
Peptide conformation and structure: Structure - activity relationship is yet another interesting area of study and research work is in progress at the Indian Institute of Technology, Mumbai, National Chemical Laboratory, Pune, Indian Association for the Cultivation of Science, Kolkata, Indian Institute of Science, Bangalore and National Institute for Pharmaceutical Education and Research, Punjab.
Peptide Biology, Drug targets, Diagnostics and immunobiology are areas of research where ICGEB, New Delhi, Dabur Research Foundation, New Delhi, Indian Institute of Technology, Kanpur, Institute of Nuclear Medicine, New Delhi, AIIMS are active.
Peptide manufacture
The manufacture of peptides and peptide based products have their presence in different countries particularly in Europe, USA and Japan. Starting from the year 1963, a major impetus for peptide research and technology innovation was provided with the development of solid phase peptide synthesizer by Dr.Bruce Merrifield. The global players in peptide manufacture are Bachem from Switzerland, US Vitamins, USA. UCB, Diosynth, Peptisyntha and Polypeptide in Europe and Mallinc Krodt in USA.
There are a few more recent entrants and the competition for peptide space seems to be hotting up. Takeda and Fujisawa in Japan are post 1990 entrants. China & South Korea also have a reasonable presence in peptide manufacture. Jupiter Bioscience Limited, Hyderabad has occupied a presence in peptides both as technology developers and manufacturers of peptide APIs' and peptide rawmaterials. Dabur India, Sun Pharma and Technoconcept have their presence in the research formulation manufacture and equipment supply respectively in India.
Peptides have been identified to play a crucial role to synthesize and manufacture novel drugs, vaccines and diagnostics to detect and treat several existing ailments and emerging problems of human and animal diseases.
Insulin, a peptide harmone, has given a boost to the prospects of peptide based drug industries. India is infact a recognized world leader for strategic research in chemical sciences and peptide constitute a very important topic of research and development. Peptide based drugs are in the market for the treatment of hormonal disorders, cardiovascular and CNS diseases and microbial infections. The need of the hour for our country is to evolve strategies for value addition to peptides synthesized and made available from research laboratories to make drugs, nutraceuticals and cosmoceuticals and performance enhancers. The peptides do have the power to usher in a revolution in health care industry across the world. Manufacturing drugs out of peptides can be both cost-effective and do not cause serious side effects when used as therapeutics in human and veterinary healthcare.
Future of peptides
The exploitation of peptides as drugs started in the early 1970's with the launching of lypressin, a vasopressin analogue by Novartis. More than 30 peptide drugs have since entered the market, the commercial opportunity realized estimated at around US dollars 5.3 billion representing 1.5 percent of the total US $ 325 billion global pharma market. The GnRG-LhRH analogues lead the peptide market followed by somatostatin, immunosupressants, hormones like calcitonin, platelet aggregate inhibitors and vasopressin. However very few innovative and pharmacologically critical peptides have reached the market in the recent years because of their fast degradation in the human and animal system, low oral absorption and bio-availability, hindrance in cross-membrane transportation, costs of Synthesis and immunogenic risks. The future R&D efforts should focus on resolving these issues. Recent research initiatives have succeeded in overcoming some of these problems as evident from the fact the peptide modifications have enhanced their bio-availability and sustained release formulation have also been developed.
Peptides activity enhancing technologies such as glycosylation, Amino acid sequence modification, pegylation and cyclisation have enhanced the interest in peptides as drugs. Recent advances in drug delivery through parenteral, mucosal, oral and transdermal routes have boosted prospects of peptides as potential drug candidates.
Peptides will continue to play a crucial and dominant role in pharmaceutical and chemical industry in view of the critical role they play in metabolic activities of humans and animals and in various other chemical reactions. India with its skilled human resource will emerge as an important centre of activity in peptide research, development and entre-preneurship.
(The author is chairman & managing director, Jupiter Biosciences)