Peptide science: A “rule model” for new generations of peptidomimetics

Reese, Hannah; Shanahan, Calvin; Proulx, Caroline; Menegatti, Stefano

doi:10.1016/j.actbio.2019.10.045

Cited by 31 publications

(21 citation statements)

References 416 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, reaching the final target with high selectivity and adequate accumulation at the target site remains a major issue for in vivo applications. Here, peptide modifications (unnatural amino acids, cyclization) and conjugate molecules (PEGylation, hydrocarbon chains) that prolong the circulation time and enhance the structural stability of nanocarriers in the serum come to mind [279,280]. Peptidomimetics, often based on natural peptide sequences, that exhibit improved proteolytic stability or even new folds and morphologies designed to enhance bio availability, improve transport through the blood-brain barrier, or reduce the rate of clearance, are emerging.…”

Section: Discussionmentioning

confidence: 99%

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Tarvirdipour

Skowicki

Schoenenberger

et al. 2021

IJMS

View full text Add to dashboard Cite

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

show abstract

Section: Discussionmentioning

confidence: 99%

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Tarvirdipour

Skowicki

Schoenenberger

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Therefore, it would be of interest to conjugate our candidate peptides with the TAT fragment ( 48 GRKKRRQRRR 57 ) or with a poly-Arginine peptide (Arg 5-8 ), either directly or through a spacer linker 46 . Other successful strategies are the conversion of the peptide with the desired biological activity into a peptoid, in which the side chain is connected to the nitrogen of the peptide backbone, instead of the α-carbon as in peptides, and other types of peptidomimetics, to improve stability and cellular uptake 47 .…”

Section: Discussionmentioning

confidence: 99%

Defined d-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease

Rapisarda

Bargiela

Llamusí

et al. 2021

Sci Rep

View full text Add to dashboard Cite

In Myotonic Dystrophy type 1 (DM1), a non-coding CTG repeats rare expansion disease; toxic double-stranded RNA hairpins sequester the RNA-binding proteins Muscleblind-like 1 and 2 (MBNL1 and 2) and trigger other DM1-related pathogenesis pathway defects. In this paper, we characterize four d-amino acid hexapeptides identified together with abp1, a peptide previously shown to stabilize CUG RNA in its single-stranded conformation. With the generalized sequence cpy(a/t)(q/w)e, these related peptides improved three MBNL-regulated exon inclusions in DM1-derived cells. Subsequent experiments showed that these compounds generally increased the relative expression of MBNL1 and its nuclear-cytoplasmic distribution, reduced hyperactivated autophagy, and increased the percentage of differentiated (Desmin-positive) cells in vitro. All peptides rescued atrophy of indirect flight muscles in a Drosophila model of the disease, and partially rescued muscle function according to climbing and flight tests. Investigation of their mechanism of action supports that all four compounds can bind to CUG repeats with slightly different association constant, but binding did not strongly influence the secondary structure of the toxic RNA in contrast to abp1. Finally, molecular modeling suggests a detailed view of the interactions of peptide-CUG RNA complexes useful in the chemical optimization of compounds.

show abstract

“…As reviewed by Collier and Segura ten years ago [ 61 ], these substances, especially the short synthetic peptides, have found increasing use as components of biomaterials within implantable devices and regenerative medicine over several decades, in order to exploit bioactivity. They are not without difficulties and disadvantages [ 62 ], particularly the fact that they can be degraded into fragments by proteolytic enzymes, and the general difficulty of persuading them to take up conformations that optimize their bioactivity [ 63 ]. Several solutions have been proposed to overcome these problems.…”

Section: Categories Of Bioactive Materialsmentioning

confidence: 99%

“…Several solutions have been proposed to overcome these problems. Reese et al discuss the development of what they refer to as peptidomimetics, which are sequence-controlled molecules that exhibit different folds and morphologies that create new structures and functions which mimic the natural peptides [ 63 ]. Alternatively, molecules may be synthesized with combinations of peptide sequences with complementary or synergistic effects so that they can address more than one biological target at the biomaterial surface [ 64 ].…”

Section: Categories Of Bioactive Materialsmentioning

confidence: 99%

Biocompatibility pathways and mechanisms for bioactive materials: The bioactivity zone

Williams

2022

Bioactive Materials

View full text Add to dashboard Cite

This essay analyzes the scientific evidence that forms the basis of bioactive materials, covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of biomaterials. This is a detailed assessment of performance in areas such as bone-induction, cell adhesion, immunomodulation, thrombogenicity and antimicrobial behavior. Bioactivity is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host tissue. Although the term ‘bioactive material’ is widely used and has a well understood general meaning, it would be useful now to concentrate on this interfacial region, considered as ‘ the bioactivity zone’ . Bioactivity phenomena are either due to topographical/micromechanical characteristics, or to biologically active species that are presented in the bioactivity zone. Examples of topographical/micromechanical effects are the modulation of the osteoblast – osteoclast balance, nanotopographical regulation of cell adhesion, and bactericidal nanostructures. Regulation of bioactivity by biologically active species include their influence, especially of metal ions, on signaling pathways in bone formation, the role of cell adhesion molecules and bioactive peptides in cell attachment, macrophage polarization by immunoregulatory molecules and antimicrobial peptides. While much experimental data exists to demonstrate the potential of such phenomena, there are considerable barriers to their effective clinical translation. This essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials, especially when the material is modified in a manner designed to specifically induce that activity.

show abstract

Peptide science: A “rule model” for new generations of peptidomimetics

Cited by 31 publications

References 416 publications

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Defined d-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease

Biocompatibility pathways and mechanisms for bioactive materials: The bioactivity zone

Contact Info

Product

Resources

About