Moonlighting Peptides with Emerging Function

Plaza, Jonathan G. Rodríguez; Rojas, Amanda Villalón; Herrera, Sur; Garza‐Ramos, Georgina; Torres‐Larios, Alfredo; Amero, Carlos; Granados, Gabriela Zarraga; Aguilar, María Isabel; Ortiz, María Teresa Lara; Polanco, Carlos; Uribe‐Carvajal, Salvador; Coria, Roberto; Diaz, A. F.; Bredesen, Dale E.; Castro-Obregón, Susana; Río, Gabriel del

doi:10.1371/journal.pone.0040125

Cited by 19 publications

(27 citation statements)

References 36 publications

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“…moonlighting characteristics). These moonlighting peptides have enormous therapeutic potential as single peptide may be used for multiple tasks ( 26 ). These peptides can be useful in the repositioning of peptide drugs, which have already passed toxicity and other safety tests and reduce the significant costs incurred by pharmaceutical companies during clinical trials.…”

Section: Introductionmentioning

confidence: 99%

SATPdb: a database of structurally annotated therapeutic peptides

et al. 2015

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SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics.

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Section: Introductionmentioning

confidence: 99%

SATPdb: a database of structurally annotated therapeutic peptides

et al. 2015

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“…DNA retention was around 60% in the 1:4 DNA to peptide charge ratio suggesting that only a small fraction of the positive charges in α-factor participate in DNA-binding. Adding positive charges to the N-terminus of α-factor increased its affinity for DNA, such as in the case of the Iztli peptide 1 [ 25 ]. These results indicate that increasing the number of positive charges in peptides, as it often occurs in CPP design, promotes the peptides' affinity for DNA and supports that these activities are compatible.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously reported one computational strategy to create multifunctional peptides. Our designed peptides, referred to as Iztli peptides, embed the α-factor pheromone of Saccharomyces cerevisiae within an AMP sequence [ 25 , 26 ]. The characterization of these peptides leads us to propose that cell-penetrating and antimicrobial activities are closely related, that is, the design of an AMP may be compatible with a CPP activity and vice versa .…”

Section: Introductionmentioning

confidence: 99%

Effective Design of Multifunctional Peptides by Combining Compatible Functions

et al. 2016

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Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf.

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“…Another type of peptide designed to destroy cancer cells is the hunter–killer peptide (HKP) that are short chimeric molecules (∼20 amino acids), which act as a ligand for receptors on the target cells and induces cell death via disruption of mitochondrial membranes with cytochrome-C release, caspase activation, and apoptosis [ 73 , 74 ]. These peptides consist of two fractions coupled by a linker often glycine–glycine; the first fraction (hunter: 5–10 amino acids) is designed to bind to the target cell receptor and the proapoptotic domain (killer: ∼14 amino acids) is responsible for inducing apoptosis [ 73 , 74 ]. The HKP-1 is targeted to the angiogenic vasculature of tumors and has strong anticancer activity in models of breast and prostate cancer, reducing tumor volume and metastasis and prolonging survival [ 73 ].…”

Section: Physicochemical Methods Of Rational Design Of Anticancer mentioning

confidence: 99%

Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

2020

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Peptides are naturally produced by all organisms and exhibit a wide range of physiological, immunomodulatory, and wound healing functions. Furthermore, they can provide with protection against microorganisms and tumor cells. Their multifaceted performance, high selectivity, and reduced toxicity have positioned them as effective therapeutic agents, representing a positive economic impact for pharmaceutical companies. Currently, efforts have been made to invest in the development of new peptides with antimicrobial and anticancer properties, but the poor stability of these molecules in physiological environments has triggered a bottleneck. Therefore, some tools, such as nanotechnology and in silico approaches can be applied as alternatives to try to overcome these obstacles. In silico studies provide a priori knowledge that can lead to the development of new anticancer peptides with enhanced biological activity and improved stability. This review focuses on the current status of research in peptides with dual antimicrobial–anticancer activity, including advances in computational biology using in silico analyses as a powerful tool for the study and rational design of these types of peptides.

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Moonlighting Peptides with Emerging Function

Cited by 19 publications

References 36 publications

SATPdb: a database of structurally annotated therapeutic peptides

SATPdb: a database of structurally annotated therapeutic peptides

Effective Design of Multifunctional Peptides by Combining Compatible Functions

Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

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