Muciño Gabriel, Castro-Obregón Susana, Hernandez-Pando Rogelio, Del Rio Gabriel
Department of Neurodevelopment and Physiology, Instituto De Fisiología Celular, UNAM, México, D.F, México.
Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán,", Mexico.
IUBMB Life. 2016 Apr;68(4):259-67. doi: 10.1002/iub.1483. Epub 2016 Mar 10.
The emergence of complex diseases is promoting a change from one-target to multitarget drugs and peptides are ideal molecules to fulfill this polypharmacologic role. Here we review current status in the design of polypharmacological peptides aimed to treat complex diseases, focusing on tuberculosis. In this sense, combining multiple activities in single molecules is a two-sided sword, as both positive and negative side effects might arise. These polypharmacologic compounds may be directed to regulate autophagy, a catabolic process that enables cells to eliminate intracellular microbes (xenophagy), such as Mycobacterium tuberculosis (MBT). Here we review some strategies to control MBT infection and propose that a peptide combining both antimicrobial and pro-autophagic activities would have a greater potential to limit MBT infection. This endeavor may complement the knowledge gained in understanding the mechanism of action of antibiotics and may lead to the design of better polypharmacological peptides to treat complex diseases such as tuberculosis.
复杂疾病的出现正推动着药物从单靶点向多靶点转变，而肽是发挥这种多药理学作用的理想分子。在此，我们综述了旨在治疗复杂疾病的多药理学肽设计的现状，重点关注结核病。从这个意义上讲，在单一分子中结合多种活性是一把双刃剑，因为可能会产生正面和负面的副作用。这些多药理学化合物可用于调节自噬，这是一种分解代谢过程，使细胞能够清除细胞内微生物（异噬作用），如结核分枝杆菌（MTB）。在此，我们综述了一些控制MTB感染的策略，并提出一种兼具抗菌和促自噬活性的肽在限制MTB感染方面具有更大的潜力。这一努力可能会补充我们在理解抗生素作用机制方面所获得的知识，并可能有助于设计出更好的多药理学肽来治疗结核病等复杂疾病。
