Antibiotic resistance is currently one of the most significant public health concerns. The World Health Organ- ization recently identified antimicrobial resistance as one of the three greatest threats facing mankind in the 21st century. Cationic host-defense peptides (HDPs) are small cationic amphiphilic peptides, and are an an- cient and vital part of the innate immune system. However, HDPs have significant drawbacks such as suscep- tibility to enzymatic degradation, low-to-moderate activity and their inconvenient optimization. We have recently developed a new class of sequence-specific peptidomimetics termed ??-AApeptides?. In ad- dition to their intrinsic advantages including enhanced stability against proteolysis and limitless potential for chemical modification, some potent molecules display broad-spectrum antimicrobial activity, and do not induce apparent resistance in drug-resistant pathogens. Furthermore, they can also modulate immune responses and show strong anti-inflammatory activity. In addition, one lead compound has shown potent in vivo activity against MRSA in mouse model. Our preliminary data suggest that antimicrobial ?-AApeptides mimic the global structure, function and mechanism of AMPs. These findings strongly suggest ?-AApeptides may be a new ap- proach for antibiotic development. The objective here, is to synthesize, develop and evaluation of more potent analogs of previously designed antimicrobial cyclic-lipidated ?-AApeptides. We will design and synthesize nov- el analogs of previously designed antimicrobial cyclic-lipidated ?-AApeptides, including cyclic-lipidated ?- AApeptides with different length of alkyl tails, diverse cationic and hydrophobic groups and expansion of cyclic- lipidated ?-AApeptides to new classes of cyclic-lipidated peptidomimetics with novel backbones. All the pep- tides need to be analyzed and purified by HPLC. Thus, a HPLC equipped with both analytical and preparative modules (Waters 1525EF) extremely critical for our proposed research.
Antibiotic resistance is currently one of the most significant public health concerns. We will design and syn- thesize novel analogs of previously designed antimicrobial cyclic-lipidated ?-AApeptides. A HPLC equipped with both analytical and preparative modules (Waters 1525EF) extremely critical for our proposed research.
| Bolarinwa, Olapeju; Zhang, Meng; Mulry, Erin et al. (2018) Sulfono-?-AA modified peptides that inhibit HIV-1 fusion. Org Biomol Chem 16:7878-7882 |
| She, Fengyu; Teng, Peng; Peguero-Tejada, Alfredo et al. (2018) De Novo Left-Handed Synthetic Peptidomimetic Foldamers. Angew Chem Int Ed Engl 57:9916-9920 |
| Li, Chunhui; Teng, Peng; Peng, Zhong et al. (2018) Bis-Cyclic Guanidines as a Novel Class of Compounds Potent against Clostridium difficile. ChemMedChem 13:1414-1420 |
| Singh, Sylvia; Nimmagadda, Alekhya; Su, Ma et al. (2018) Lipidated ?/?-AA heterogeneous peptides as antimicrobial agents. Eur J Med Chem 155:398-405 |
| Bolarinwa, Olapeju; Cai, Jianfeng (2018) Developments with investigating descriptors for antimicrobial AApeptides and their derivatives. Expert Opin Drug Discov 13:727-739 |
| Teng, Peng; Li, Chunhui; Peng, Zhong et al. (2018) Facilely accessible quinoline derivatives as potent antibacterial agents. Bioorg Med Chem 26:3573-3579 |
| Bolarinwa, Olapeju; Nimmagadda, Alekhya; Su, Ma et al. (2017) Structure and Function of AApeptides. Biochemistry 56:445-457 |
| Sui, Hua; Zhao, Jihui; Zhou, Lihong et al. (2017) Tanshinone IIA inhibits ?-catenin/VEGF-mediated angiogenesis by targeting TGF-?1 in normoxic and HIF-1? in hypoxic microenvironments in human colorectal cancer. Cancer Lett 403:86-97 |
| Shi, Yan; Challa, Sridevi; Sang, Peng et al. (2017) One-Bead-Two-Compound Thioether Bridged Macrocyclic ?-AApeptide Screening Library against EphA2. J Med Chem 60:9290-9298 |
| Teng, Peng; Ma, Ning; Cerrato, Darrell Cole et al. (2017) Right-Handed Helical Foldamers Consisting of De Novo d-AApeptides. J Am Chem Soc 139:7363-7369 |
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