Variants of self-assembling peptide, KLD-12 that show both rapid fracture healing and antimicrobial properties

Tripathi, Jitendra Kumar; Pal, Subhashis; Awasthi, Bhanupriya; Kumar, Amit; Tandon, Anshika; Mitra, Kalyan; Chattopadhyay, Naibedya; Ghosh, Jimut Kanti

doi:10.1016/j.biomaterials.2015.03.046

Cited by 75 publications

(49 citation statements)

References 31 publications

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“…Besides synthetic approaches, mimicking the structure and function of antimicrobial peptides (AMPs) that occur naturally can provide new insights into the design of effective antibacterial hydrogels . AMPs are cationic and water soluble peptides produced by many species, including plants and animals, which exhibit strong antibacterial activity against a broad spectrum of microorganisms .…”

Section: Introductionmentioning

confidence: 99%

O‐Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies

Liang

Yan

et al. 2019

Macromolecular Bioscience

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Multivalent carbohydrate–lectin interactions play a crucial role in bacterial infection. Biomimicry of multivalent glycosystems represents a major strategy in the repression of bacterial growth. In this study, a new kind of glycopeptide (Naphthyl‐Phe‐Phe‐Ser‐Tyr, NMY) scaffold with mannose modification is designed and synthesized, which is able to perform supramolecular self‐assembly with the assistance of catalytic enzyme, and present multiple mannose ligands on its self‐assembled structure to target mannose‐binding proteins. Relying on multivalent carbohydrate–lectin interactions, the glycopeptide hydrogel is able to bind Escherichia coli (E. coli) in high specificity, and result in bacterial adhesion, membrane disruption and subsequent cell death. In vivo wound healing assays reveal that this glycopeptide hydrogel exhibits considerable potentials for promoting wound healing and preventing E. coli infection in a full‐thickness skin defect mouse model. Therefore, through a specific mannose–lectin interaction, a biocompatible hydrogel with inherent antibacterial activity against E. coli is achieved without the need to resort to antibiotic or antimicrobial agent treatment, highlighting the potential role of sugar‐coated nanomaterials in wound healing and control of bacterial pathogenesis.

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Section: Introductionmentioning

confidence: 99%

O‐Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies

Liang

Yan

et al. 2019

Macromolecular Bioscience

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“…Peptide synthesis was done manually utilizing a solid-phase method on rink amide MBHA resin and Fmoc chemistry as described previously (8,11,(16)(17)(18)(19)(20). Labeling of the peptides at their N termini by NBD was achieved by the usual procedure, as described earlier (21).…”

Section: Methodsmentioning

confidence: 99%

“…To examine the cytotoxicity of the peptides, the viability of murine NIH 3T3 cells was determined by a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay as described earlier (17,21,24).…”

Section: Methodsmentioning

confidence: 99%

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

Kumar

Tripathi

Kathuria

et al. 2016

Antimicrob Agents Chemother

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dPiscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with significant antimicrobial and antiendotoxin activities can be designed by incorporating single alanine substitutions in the piscidin-1 heptad repeat. Fish antimicrobial peptide (AMP) piscidin-1, which was discovered in 2001, possesses versatile biological activities. Piscidin-1 shows significant activity against bacteria, fungi, parasites, and cancer cells (1-7). It can also neutralize lipopolysaccharide (LPS)-induced proinflammatory responses in macrophage cells (5). Along with these desired biological activities, piscidin-1 also exhibits very significant lytic activity against normal mammalian cells, which is an obstacle for employing it as a lead molecule for the development of a new antimicrobial agent. Therefore, deciphering of the basis of cytotoxicity in piscidin-1 and the design of nontoxic analogs of piscidin-1 with desired biological activity were the objectives of the present investigation. Toward this end, we intended to identify the important primary sequence in piscidin-1 that could have a strong impact on its structural, functional, and ...

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“…25 Total RNA from snap-frozen knee joints was extracted in Trizol. 25 Total RNA from snap-frozen knee joints was extracted in Trizol.…”

Section: Qpcrmentioning

confidence: 99%

“…qPCR was performed as described before. 25 Total RNA from snap-frozen knee joints was extracted in Trizol. qPCR was performed by SYBR green dye using gene-specific primer pairs listed in Table 1.…”

Section: Qpcrmentioning

confidence: 99%

Fasciola helminth defense molecule‐1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response

et al. 2019

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An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKLinduced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.

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Variants of self-assembling peptide, KLD-12 that show both rapid fracture healing and antimicrobial properties

Cited by 75 publications

References 31 publications

O‐Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies

O‐Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

Fasciola helminth defense molecule‐1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response

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