A pinboard by
Ruchi Omar

Research Scholar , Department of Chemistry, University Institute of Engineering and Technology, CSJM University, Kanpur 208024


To design a non toxic peptidomimitic drug to treat HIV and internal fungal infection

Antifungal agents are of great importance from different perspectives. Prime usage in human as a medication to treat and prevent mycosis such as athlete’s foot, candidiasis, serious systematic infections like cryptococcal meningitis, etc. Antifungal agents come in different preparations as creams, sprays, shampoos, pessaries, oral tablets etc.Terbinafine, fluconazole and few more can be orally taken to treat fungal infections within the body. Only in case of serious fungal infection antifungals like amphotericin, itraconazole, etc. are injected intramuscular or intravenous. Topical preparations of antifungal agents usually cause no side effects. Few common side effects of oral antifungals are nausea, headache, diarrhea. The antifungals given through injection cause serious problems and are administered only when the need for treatment outweighs their risk (R. Omar, S. Sharma and A. Yadav, WJPPS, 5(9): 591, 2016). People with poor immune system, for example, people undergoing chemotherapy or treatment for HIV/AIDS are constantly at risk of developing internal fungal infection and are thus regularly prescribed antifungal medications. Several classes of antifungal agents have been developed to combat ever increasing cases of resistant strains of fungi. Azoles, despite being the most popular clinical choice, are not devoid of side effects. Many antimicrobial peptides have also been tested in search of safe, nontoxic antifungals but none succeeded as a commercial alternative. Recent research attempts show continued interest in these compounds and the complexities associated. Some experimental observations indicate involvement of these antimicrobial peptides in enhancing the efficacy of anti-HIV agents. I have studied an intertwined approach to deal with two fatal diseases, internal fungal infection and HIV infection. Several naturally occurring antimicrobial peptides have been studied for their possible interaction with the viral RNA primer binding site (template) through interactions other than the base pair – base pair type. Peptides have been prepared and docked into viral template utilizing extra precision, flexible ligand docking. Implicit solvent was added around the complex and MMGBSA interaction energies were computed. Druggability aspects were explored by calculating ADME-related properties. The designed peptidomimetic lead compound may help in obtaining nontoxic anti-HIV agents in the future ( R. Omar, A. Yadav, Can. J. Chem., 95(6): 633, 2017).


Purification and characterization of antimicrobial peptides from the skin secretion of Rana dybowskii.

Abstract: Six antimicrobial peptides designated dybowskins were isolated from the skin secretion of Rana dybowskii, an edible frog in Korea. Dybowskin-1 (FLIGMTHGLICLISRKC) and dybowskin-2 (FLIGMTQGLICLITRKC) were isoforms differing in only two amino acid residues at the 7th and 14th positions from the N-terminus, and they showed amino acid sequence similarities with ranalexin peptides. Dybowskin-3 (GLFDVVKGVLKGVGKNVAGSLLEQLKCKLSGGC), dybowskin-4 (VWPLGLVICKALKIC), dybowskin-5 (GLFSVVTGVLKAVGKNVAKNVGGSLLEQLKCKISGGC), and dybowskin-6 (FLPLLLAGLPLKLCFLFKKC) differed in both size and sequence, and they were, in terms of amino acid sequence similarities, related to brevinin-2, japonicin-2, esculentin-2, and brevinin-1 peptides, respectively. All the peptides presented in this paper contained Rana-box, the cyclic heptapeptide domain, which is conserved in other antimicrobial peptides derived from the genus Rana. All the dybowskin peptides showed a broad spectrum of antimicrobial activity against the Gram-positive and Gram-negative bacteria (minimum inhibition concentrations (MIC), 12.5 to >100 microg/ml) and against Candida albicans (MIC, 25 to >100 microg/ml). Especially, dybowskin-4 with valine at its N-terminus was the most abundant and showed the strongest antimicrobial activity among all the dybowskin peptides. This result indicates that the dybowskin peptides from R. dybowskii, whose main habitats are mountains or forests, have evolved differently from antimicrobial peptides isolated from other Korean frogs, whose habitats are plain fields.

Pub.: 21 Aug '07, Pinned: 03 Jul '17

Cathelicidin-derived Trp/Pro-rich antimicrobial peptides with lysine peptoid residue (Nlys): therapeutic index and plausible mode of action.

Abstract: Recently, we designed a novel cell-selective antimicrobial peptide (TPk) with intracellular mode of action from Pro --> Nlys (Lys peptoid residue) substitution in a noncell-selective cathelicidin-derived Trp/Pro-rich antimicrobial peptide, tritrpticin-amide (TP; VRRFPWWWPFLRR-NH(2)) (Biochemistry 2006; 45: 13007-13017). In this study, to elucidate the effect of Pro --> Nlys substitution on therapeutic index and mode of action of other noncell-selective cathelicidin-derived Trp/Pro-rich antimicrobial peptides and develop novel short antimicrobial peptides with high cell selectivity/therapeutic index, we synthesized Nlys-substituted antimicrobial peptides, TPk, STPk and INk, in which all proline residues of TP, symmetric TP-analogue (STP; KKFPWWWPFKK-NH(2)) and indolicidin (IN; ILPWKWPWWPWRR-NH(2)) were replaced by Nlys, respectively. Compared to parent Pro-containing peptides (TP, STP and IN), Nlys substituted peptides (TPk, STPk and Ink) had 4- to 26-fold higher cell selectivity/therapeutic index. Parent Pro-containing peptides induced a significant depolarization of the cytoplasmic membrane of intact Staphylococcus aureus at their MIC, whereas Nlys-substituted antimicrobial peptides did not cause visible membrane depolarization at their MIC. These results suggest that the antibacterial action of Nlys-substituted peptides is probably not due to the disruption of bacterial cytoplasmic membranes but the inhibition of intracellular components. Taken together, our results showed that Pro --> Nlys substitution in other noncell-selective Trp/Pro-rich antimicrobial peptides such as STP and IN as well as TP can improve the cell selectivity/therapeutic index and change the mode of antibacterial action from membrane-disrupting to intracellular targeting. In conclusion, our findings suggested that Pro --> Nlys substitution in noncell-selective Trp/Pro-rich antimicrobial peptides is a promising method to develop cell-selective antimicrobial peptides with intracellular target mechanism.

Pub.: 03 Jul '07, Pinned: 03 Jul '17

Cell selectivity and mechanism of action of short antimicrobial peptides designed from the cell-penetrating peptide Pep-1.

Abstract: Pep-1-K (PK) is a good cell-selective antimicrobial peptide designed from cell-penetrating peptide Pep-1. To develop novel short antimicrobial peptides with higher cell selectivity and shorter length compared with PK, several PK analogs were designed by the deletion, addition and/or substitution of amino acids. Among these analogs, PK-12-KKP (KKPWWKPWWPKWKK) showing the sequence and structure homology with a Trp/Pro-rich natural antimicrobial peptide, indolicidin (IN), displayed a 20-fold higher cell selectivity as compared to IN. Circular dichroism analysis revealed that PK-12-KKP adopts a folded structure combined with some portions of unordered structure. PK-12-KKP selectively binds to negatively charged bacterial membrane-mimetic vesicles, and its high phospholipid selectivity corresponds well with its high cell selectivity. Moreover, it showed very weak potential in depolarization of the cytoplasmic membrane of Staphylococcus aureus at 8 microM (4x minimal inhibitory concentration) and dye leakage from negatively charged liposomes. These results suggest that the ultimate target of our designed PK-12-KKP maybe the intracellular components (e.g. protein, DNA or RNA) rather than the cytoplasmic membranes. Collectively, our designed short Trp/Pro-rich peptide, PK-12-KKP, appears to be an excellent candidate for future development as a novel antimicrobial agent.

Pub.: 21 May '09, Pinned: 03 Jul '17