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Botulinum toxins: Pharmacology, immunology, and current developments
Published in Anthony V. Benedetto, Botulinum Toxins in Clinical Aesthetic Practice, 2017
BoNT types A and E cleave SNAP-25 at different sites, and the effects of type E are much shorter. Evidence indicates that the type A light chain and its cleavage product (SNAP-25197) localize to the plasma membrane, whereas the type E light chain is distributed throughout the cell cytoplasm.44 The localization of type A light chain to the plasma membrane is decreased following mutation of the dileucine motif. Mutation of the dileucine motif of type A also leads to rapid recovery of neuromuscular function in rats.45 More recently, mutation of the two leucines has been found to prevent interactions between the light chain and septins—intracellular structural proteins found clustered with the light chain at the plasma membrane (Figure 2.5).46 The dileucine mutation also increases degradation of the type A light chain, as does interference with light chain-septin clustering. In contrast, the type E light chain does not interact with septins. These data indicate that the clustering of the type A light chain with septins at the plasma membrane via interactions with the dileucine motif is critical for its stability; these characteristics importantly contribute to the duration of action of BoNTA in clinical use.44,46 Type A is the only botulinum neurotoxin serotype that contains a dileucine motif at the C terminus of the light chain.44
Abies Spectabilis (D. Don) G. Don (Syn. A. Webbiana Lindl.) Family: Coniferae
Published in L.D. Kapoor, Handbook of Ayurvedic Medicinal Plants, 2017
Chemical constituents — The edible fruit contains free amino acids: arginine, glycine, threonine, glutamic acid, leucines. The ripe seeds contain bitter principles — cucurbitacins — B, D, G, H. The roots contain cucurbitacin B and traces of G. Chemical examination of seeds showed the presence of the crystalline bitter principle cucurbitacin B and oleanolic acid. Ripe seeds yield 19.9% oil.178
Using peptides to promote delivery and improve anti-tumour efficacy of liposomal drug
Published in Journal of Drug Targeting, 2022
Possible explanations for the apparent lack of effect of engrafted pCD47 on the lifetime of liposomes in the blood include the following: Firstly, it is possible that the hydrophobic nature of pCD47 (which contains two leucines, two isoleucines, a tyrosine, a valine, and a cysteine) may have promoted hydrophobic interaction between pCD47-liposomes leading to liposome aggregation [39]. This could result in an enhanced elimination of liposome aggregates by the filtration effects of various tissues, such as the liver and spleen; or may become trapped in the capillary beds of the lungs [40,41]. Whilst no evidence of aggregation was found during liposome size measurements (Table 2), our observation that overnight storage of the pCD47-DiR-liposomes at 4 °C resulted in a bluish (due to the DiR) precipitate/aggregate at the bottom of the tube (not shown), lends support to this possibility. Secondly, the highly hydrophobic nature of pCD47 may result in the peptide becoming partially embedded within the liposome bilayer, thus potentially interfering with the ability of the engrafted pCD47 to interact with its target receptor (SIRP-α). Clearly, a combination of the above two possibilities is also possible.
New designed pH-responsive histidine-rich peptides with antitumor activity
Published in Journal of Drug Targeting, 2021
Linlin Chang, Hexin Bao, Jia Yao, Hui Liu, Sanhu Gou, Chao Zhong, Yun Zhang, Jingman Ni
The short peptide LK (LKKLLKLLKKLLKL-NH2) is a cationic amphiphilic peptide with a significant antimicrobial activity [24]. Our pre-experiment results showed that LK exhibited a high cytotoxic activity against tumour cells as well. However, the damage to normal cells at concentrations which close to its effective concentrations would narrow its therapeutic index. Here, we used the acidic tumour microenvironment as a trigger to design a series of new acid-activated anticancer peptides that were less active or not active under physiological conditions. We substituted all the lysines of LK with histidines and adopted the different distributions of histidines and leucines to generate a series of new histidine-rich peptides (Table 1). Through this design, we expected to achieve a desirable acid-activate anticancer peptide, which could kill tumour cells more effectively than their parental peptide LK while maintaining the minimal toxicity to normal tissue. The structural properties of the new peptide analogs were determined and compared in this study. The pH-responsive antitumor activity was evaluated in vitro. Moreover, in order to better understand the antitumor activity towards cancer cells, the antitumor mechanism of the better analog was further investigated.
Drug discovery through the isolation of natural products from Burkholderia
Published in Expert Opinion on Drug Discovery, 2021
Adam Foxfire, Andrew Riley Buhrow, Ravi S. Orugunty, Leif Smith
Icosalides: B. gladioli BCC0238 also produces a two-tailed lipopeptidiolide antibiotic known as icosalide A1. This compound was also isolated from Burkholderia gladioli HKI0739 by Dose et al. [58]. Structurally these compounds are cyclic lipopeptidiolides that are made up of two serines, two leucines, one 3-hydroxy octanoic acid, and one 3-hydroxy decanoic acid moiety joined by amide and ester linkages (Figure 3(b, c)). This compound was originally reported to have been isolated from a fungal culture (Aureobasidium species). However, the origin was later determined to be bacterial. It was hypothesized that a bacterium (Burkholderia gladioli strain) was associated with the original fungal isolate [58,59].