Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms22168677
Keywords
retro-inverso peptides; anticancer peptides; drug delivery; peptide antigens; A beta; IAPP; antimicrobial peptides
Funding
- Regione Campania
- MUR [PRIN 2017M8R7N9]
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Retro-inverso peptides, possessing reversed sequences and chirality compared to parent molecules, show promise as more stable surrogates with increased potential as drugs, especially in specific cases. However, their inability to adopt the 3D structure of parent peptides requires careful evaluation and investigation of their applications on a case-by-case basis.
Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.
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