spacer
home > ebr > spring 2009 > optimised therapeutic peptides - from sequence to drug
PUBLICATIONS
European Biopharmaceutical Review

Optimised Therapeutic Peptides - From Sequence to Drug

 

BENEFITS AND LIMITATIONS OF THERAPEUTIC PEPTIDES

Over the last 10 years, many synthetic peptide-based drug products have entered the market as therapeutic agents. Peptides that are finally approved as drugs, such as Fuzeon (Roche), demonstrate the enormous potential that peptides have. Currently, many peptide-based drugs are in clinical or registration phases.

Screening current research literature, there are certainly many peptides that have potential biological activity and could be used as drugs. However, most of them never make it to the early stages of development: only 1.5 per cent of drug candidates will find their way from target identification to approval (1). This is mainly due to their inherent instability/degradability in biological systems, and the unfavourable pharmacokinetic properties of the class.

A rate of 1.5 per cent is high compared to the success of small drugs, but still does not reflect the enormous advances in peptide chemistry and purification of the last decades. This review summarises the exciting potential of the entire field of peptide-drugs, and shows how stateof-the-art peptide engineering can overcome the class limitations of peptides in many cases.

OBJECTIVES OF PEPTIDE OPTIMISATION

The major incentive for the modification of peptides is their potential for major market share in blockbuster indications (such as Affymax: Hematide and Roche: Enfuvirtide). However, the body presents many barriers to the entry of peptides. Peptides do not usually cross biological membranes readily; they are metabolised by proteolytic enzymes and are rapidly excreted through the liver and kidneys.

As a consequence, many natural peptides suffer from low bioavailability and a short biological half-life. Besides the issue of proteolytic instability, there is also the problem of structural instability. Peptides are much smaller than proteins and, for this reason, are structurally less stable, due to their smaller number of intramolecular interactions. Besides improvement in protease resistance, peptides can also need structural stabilisation measures, such as helical constraints, in order to end up with a reasonable specificity and affinity. The primary objective of pharmacological peptide optimisation is to develop analogues that can overcome the problems and barriers related to peptides, while retaining or even enhancing selective activity, usually based on a thorough understanding of the structure-activity relationship. This design-based strategy of peptide optimisation – which is nothing but a high-tech engineering approach –


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer

Dr Udo Haberl is Director of Drug Design at AplaGen GmbH. He obtained a PhD from the University of Bonn, specialising in theoretical organic chemistry and the development of anti-cancer drugs. He has developed molecular modelling software and worked at the University of Notre Dame (US) and at various biotech companies, where he gained more than 10 years’ experience in the design of pharmaceutical drugs. At AplaGen, he is focusing on design and optimisation of peptide sequences, linker structures and new technologies for peptide stabilisation.

Dr Andreas Rybka is Director of Peptide Chemistry at AplaGen GmbH. He obtained a PhD from the University of Bochum, specialising in the synthesis and conformational analysis (NMR, molecular modelling) of peptides. Andreas has 10 years’ experience in the synthesis, purification and structural analysis of peptides and proteins. At AplaGen, he focuses on the synthesis and purification of peptides and new technologies for peptide synthesis.

Prof Dr Hans-Georg Frank is CEO and co-founder of AplaGen GmbH. He is a physician, and obtained his PhD/MD from the Free University of Berlin. He worked at the Free University of Berlin and the University of Technology in Aachen, Germany, where he focused on embryology, developmental biology and oncological topics. Besides working as an academic scientist, he has also managed clinical studies at Sandoz AG in Nürnberg, Germany. During his academic career, he was awarded large grants from The Rockefeller Foundation and WHO, as well as from the German Research Council, and has published more than 50 articles in peer-reviewed journals. He was appointed Professor at the University of Technology in Aachen.

spacer
Udo Haberl
spacer
spacer
spacer
Andreas Rybka
spacer
spacer
spacer
Hans-Georg Frank
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Avacta and Cytiva collaborating on COVID-19 rapid test

Cambridge and Wetherby, UK, 08 April 2020: Avacta Group plc (AIM: AVCT), the developer of Affimer® biotherapeutics and reagents, is pleased to announce that it has entered into a collaboration with Cytiva, formerly known as GE Healthcare Life Sciences. The companies will develop and manufacture an Affimer-based point-of-care rapid test intended for screening of large populations to diagnose the COVID-19 coronavirus infection.
More info >>

White Papers

Working Towards a Standardised Identification Solution

PCI Pharma Services

The security of the pharmaceutical supply chain is an issue of growing concern, with recent reports addressing its vulnerability to counterfeiting. The complexity of the European supply chain is one of the key factors of this counterfeiting pandemic, with millions of medicine packs being moved around the EU, annually. Aside from this, fragmentation has resulted in decreased transparency in the supply chain and increased difficulties to track and trace medicines, leading to significant threat from counterfeiting. As a key source of income for the European economy, it is essential that the supply chain remains safe and free of counterfeits. A significant stumbling block within the industry remains to be the lack of a unified, single‐source pan‐European or indeed global database where scanned bar codes on drug packaging can be verified at point of dispense. At some point in the future the pharmaceutical industry, regulatory bodies, clinicians and retailers will need to join forces to overcome this.
More info >>

 
Industry Events

World Vaccine Congress Washington

27-29 September 2020, Walter E Washington Convention Center, Washington, US

The World Vaccine Congress is an award-winning series of conferences and exhibitions that have grown to become the largest and most established vaccine meeting of its kind across the globe. Our credibility is show through the prestigious scientific advisory board that spend months of hard work creating a new and topical agenda, year on year.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement