Sharma Komal, Aaghaz Shams, Shenmar Kitika, Jain Rahul
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160062, India.
Recent Pat Antiinfect Drug Discov. 2018;13(1):12-52. doi: 10.2174/1574891X13666180628105928.
After the era of serendipitous discovery of penicillin and outburst in the discovery and development of highly efficient antibiotics, a surge in resistance against the target specific drugs was observed, primarily due to a combination of selective pressure of antibiotics use and spontaneous mutations. As per the World Health Organization, antibiotic resistance is one of the greatest threats to the mankind.
Short antimicrobial peptides (SAMPs) can be considered as a viable therapeutic alternative to conventional antibiotics in tackling resistant microbes. The ubiquitous nature of SAMPs combined with their ability to act via non-specific modes of action, high activity against a wide spectrum of drug-sensitive and drug-resistant microbes, and relative insusceptibility against the development of resistance adds to their desirability as new generation antibiotics.
Due to the natural tendency of peptides to get metabolized by proteolytic enzymes, modification of naturally occurring SAMPs is desirable. The modifications can be done either by incorporating unnatural or modified amino acids into the peptide chain or by protecting C and N termini. The characteristic feature of SAMPs is their hydrophobicity and cationicity, which aid in the effective killing of microbes by selectively binding target and lysing the microbial cells with less deleterious effects on the host cells as compared to AMPs and other conventional antibiotics.
Herein, we discussed the arsenal of short peptides and peptidomimetics starting from the smallest unit possible - a dipeptide to a decapeptide along with their activity profiles as antimicrobials. Recently, various SAMPs have paved their ways from in vitro studies to clinical trials, as evident from the most recent patent (EP1951194) on oral hygiene. This step by step growth of SAMPs has restored the hope in peptide-based therapeutics, which may prove an essential tool in eradicating antimicrobial resistance and tackling various microbial infections.
在青霉素偶然发现的时代以及高效抗生素的发现和开发热潮之后，人们观察到对靶向特定药物的耐药性激增，这主要是由于抗生素使用的选择性压力和自发突变共同作用的结果。根据世界卫生组织的说法，抗生素耐药性是对人类最大的威胁之一。
短抗菌肽（SAMPs）可被视为在应对耐药微生物方面替代传统抗生素的可行治疗选择。SAMPs的普遍存在，加上它们通过非特异性作用模式发挥作用的能力、对多种药物敏感和耐药微生物的高活性以及相对不易产生耐药性，增加了它们作为新一代抗生素的吸引力。
由于肽天然容易被蛋白水解酶代谢，因此对天然存在的SAMPs进行修饰是可取的。修饰可以通过将非天然或修饰的氨基酸掺入肽链中，或者通过保护C端和N端来实现。SAMPs的特征是它们的疏水性和阳离子性，这有助于通过选择性结合靶标并裂解微生物细胞来有效杀死微生物，与抗菌肽和其他传统抗生素相比，对宿主细胞的有害影响较小。
在此，我们讨论了从最小的单位——二肽到十肽的短肽和肽模拟物库及其作为抗菌剂的活性概况。最近，各种SAMPs已经从体外研究进入临床试验，从关于口腔卫生的最新专利（EP1951194）中可以明显看出。SAMPs的这一步一步的发展恢复了基于肽的治疗方法的希望，这可能证明是消除抗菌耐药性和应对各种微生物感染的重要工具。
