Understanding collagen interactions and their targeted regulation by novel drugs

ABSTRACT

Introduction: Among protein and fibers in the extracellular matrix (ECM), collagen is the most copious and widely employed in cosmetic, food, pharmaceutical, and biomedical industries due to its extensive biocompatible and versatile properties. In the last years, the knowledge about functions of collagens increased and expanded dramatically. Once considered only crucial for the ECM scaffolding and mechanotransduction, additional functional roles have now been ascribed to the collagen superfamily which are defined by other recently discovered domains, supramolecular assembly and receptors.

Areas covered: Given the importance of each step in the collagen biosynthesis, folding and signaling, medicinal chemists have explored small molecules, peptides, and monoclonal antibodies to modulate enzymes, receptors and interactions with the physiological ligands of collagen. These compounds were also explored toward diseases and pathological conditions. The authors discuss this providing their expert perspectives on the subject area.

Expert opinion: Understanding collagen protein properties and its interactome is beneficial for therapeutic drug design. Nevertheless, compounds targeting collagen-based interactome suffered from the presence of different isoforms for each target and the lack of specific 3D crystal structures able to guide properly drug design.

KEYWORDS:

• Collagen
• interactions
• drug design
• drug target
• integrin
• discoidin
• metalloproteinase
• collagen prolyl-4-hydroxylase

Article highlights

• Functions of the superfamily of collagens are not confined to extracellular matrix scaffolding and mechanotransduction given to the presence of additional functional protein domains and supramolecular assembly.

• After protein translation, collagen prolyl 4-hydroxylases and lysyl oxidases finely regulate modifications of amino acid residues and are thus considered as a crucial therapeutic target.

• Receptor/enzyme-mediated interactions and signaling of collagen have a pivotal role in several diseases and represent a potential target for therapy.

• Small molecules and monoclonal antibodies were explored to modulate the enzymes, receptors and interactions with the physiological ligands of collagen.

• Structure-Activity Relationship studies within each class of published or licensed compounds were provided to enhance the drug design.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.