Discovery of Peptide Drugs from Natural Sources

Henriques, Sónia Troeira; Craik, David J.

doi:10.1002/9781118995303.ch6

Cited by 2 publications

(1 citation statement)

References 302 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several synthetic cyclotides have also been made for applications in drug design. The first cyclotides were generated during the rise of natural products through their discovery as active compounds in studies that screened plant extracts for medicinal properties [ 35 , 36 , 37 , 38 ]. They were initially discovered because of their uterotonic activity by identifying Kalata B1 as an active agent from Oldenlandia affinis , thus used in African traditional medicine as a utertonic tea to quicken childbirth [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV

Ebenezer

Damoyi

Shapi

et al. 2023

JFB

View full text Add to dashboard Cite

Microtubules are cylindrical protein polymers assembled in the cytoplasm of all eukaryotic cells by polymerization of aβ tubulin dimers, which are involved in cell division, migration, signaling, and intracellular traffic. These functions make them essential in the proliferation of cancerous cells and metastases. Tubulin has been the molecular target of many anticancer drugs because of its crucial role in the cell proliferation process. By developing drug resistance, tumor cells severely limit the successful outcomes of cancer chemotherapy. Hence, overcoming drug resistance motivates the design of new anticancer therapeutics. Here, we retrieve short peptides obtained from the data repository of antimicrobial peptides (DRAMP) and report on the computational screening of their predicted tertiary structures for the ability to inhibit tubulin polymerization using multiple combinatorial docking programs, namely PATCHDOCK, FIREDOCK, and ClusPro. The interaction visualizations show that all the best peptides from the docking analysis bind to the interface residues of the tubulin isoforms αβl, αβll, αβlll, and αβlV, respectively. The docking studies were further confirmed by a molecular dynamics simulation, in which the computed root-mean-square deviation (RMSD), and root-mean-square fluctuation (RMSF), verified the stable nature of the peptide–tubulin complexes. Physiochemical toxicity and allergenicity studies were also performed. This present study suggests that these identified anticancer peptide molecules might destabilize the tubulin polymerization process and hence can be suitable candidates for novel drug development. It is concluded that wet-lab experiments are needed to validate these findings.

show abstract

Section: Resultsmentioning

confidence: 99%

A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV

Ebenezer

Damoyi

Shapi

et al. 2023

JFB

View full text Add to dashboard Cite

show abstract

Discovery, structure, function, and applications of cyclotides: circular proteins from plants

Weidmann

Craik

2016

EXBOTJ

102

View full text Add to dashboard Cite

Cyclotides are plant-derived cyclic peptides that have a head-to-tail cyclic backbone and three conserved disulphide bonds that form a cyclic cystine knot motif. They occur in plants from the Violaceae, Rubiaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, typically with 10-100 cyclotides in a given plant species, in a wide range of tissues, including flowers, leaves, stems, and roots. Some cyclotides are expressed in large amounts (up to 1g kg(-1) wet plant weight) and their natural function appears to be to protect plants from pests or pathogens. This article provides a brief overview of their discovery, distribution in plants, and applications. In particular, their exceptional stability has led to their use as peptide-based scaffolds in drug design applications. They also have potential as natural 'ecofriendly' insecticides, and as protein engineering frameworks.

show abstract

Discovery of Peptide Drugs from Natural Sources

Cited by 2 publications

References 302 publications

A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV

A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV

Discovery, structure, function, and applications of cyclotides: circular proteins from plants

Contact Info

Product

Resources

About