Abstract
Peptide-derived drugs constitute a significant fraction of therapeutic agents. In 2013, The global market of peptide therapeutics was ca. $19 billion; this value does not include revenue from insulin derivatives of $28 million. The combined sales of insulin and non-insulin peptide drugs is estimated to exceed $70 billion by 2019. A significant fraction of peptide-derived drugs is composed of an amino acid sequence and additional chemical functionalities that improve biological and pharmacological properties of the drug. In this review, we focus on synthetic cross-linkers that we refer to as “linchpins”, which are commonly used to constrain the secondary structure of peptides and equip them with added benefits such as resistance to proteolytic degradation and conformational stability. The latter property leads to an increase in binding potency and increased bioavailability due to increased permeation through biological membranes. Some linchpins can even introduce properties not found in natural peptides such as light-responsiveness. Peptides cyclized by linchpins can be viewed as a sub-class of a larger family of peptide-derived drugs with desired pharmacological performance in vivo. To understand how chemical modifications by linchpins improve drug discovery, this review also briefly summarizes canonical examples of chemical modification used in modern peptide therapeutics.
Keywords: Peptides, peptide macrocycles, side chain cross-linking, biocompatible chemistry, chemical modification of generically- encoded libraries.
Graphical Abstract
Call for Papers in Thematic Issues
Advancing the Understanding of Regulatory Mechanisms and Diseases Through Biochemistry and Structural Biology
Modern research is increasingly interested in understanding the regulatory mechanisms and diseases through various integrative approaches. Biochemistry and structural biology offer valuable atomic-level insights that help unravel the complexities of cellular regulatory mechanisms and their association with health and disease. The unique advantage of these fields is that they provide ...read more
Protein Based Biomaterials in Environmental Sustainability, Therapy, and Diagnostics
Protein-based biomaterials have wide variety of therapeutic and diagnostic applications. Important properties of these materials are biocompatibility, biodegradability, functional versatility, and ability to interact with life. They are biodegradable so make sought after targets for environmental applications. These materials are also being investigated for increased applications in water filtration technology ...read more
Recent Advances in Protein Engineering and Design
Protein engineering and design have revolutionized biotechnology, medicine, and industrial applications by enabling the creation of novel proteins with tailored functions. Recent advancements in computational modeling, directed evolution, and synthetic biology have expanded the possibilities for engineering proteins with enhanced stability, specificity, and activity. This special issue will explore state-of-the-art ...read more
Therapeutic Proteins and Peptides of Plant Origin
Plants are still the major repository of biologically active substances. In the last two decades, however, natural peptides and proteins of plant origin have gained increasing attention due to their pharmacological activities over a variety of human illnesses, including those mediated by infections and parasitosis and those involving different cellular ...read more
Related Books
Microbial Insights into Wastewater Treatment and Environmental Sustainability
Biological Control for Plant Protection: Recent Advances in Research and Sustainability
From Genes to Algorithms: Navigating the Biotechnology Data Revolution
Phytochemical Arsenal: Understanding Plant Defense Mechanisms Against Nematodes
Controlled Environment Horticulture: Where Plant Biotechnology Meets Sustainable Future
Genetic Diversity of Coronaviruses: From SARSCoV to SARS-CoV-2 – (Part 2)
Wild Vegetables: Morphology, Phytochemistry and Utility - (Part 2)
A Practical Approach to Molecular Cloning
Organoid Technology: Disease Modelling, Drug Discovery, and Personalized Medicine
Arid and Semi-Arid Zones of Mexico: A Comprehensive Exploration of Biodiversity, Ecology, and Conservation
82
3