Transformation of Natural Products by Marine-Derived Microorganisms
Se-Kwon Kim in Marine Biochemistry, 2023
Some examples of terpenoid biotransformation that have been described in the literature will be presented below. The marine bacteria Vibrio cholerae, Listonella damsela, and Vibrio alginolyticus, isolated from sediments of Daya Bay (China), were used in the biotransformation of D-limonene. The biotransformation experiments were carried out in liquid culture medium containing peptone and yeast extract as carbon and nitrogen sources. These experiments were incubated in an orbital shaker (120 rpm, 28°C) for 6 days. Different compounds were identified by gas chromatography-mass spectrometry (GC-MS), including possible biotransformation products (Figure 5.1). Furthermore, sesquiterpenes and triterpenes were identified, which were not detected in the control experiments. Houjin and co-workers believe that the presence of D-limonene activates the biosynthetic pathways of other terpenoids (Houjin et al., 2006).
Affinity Labeling
Roger L. Lundblad, Claudia M. Noyes in Chemical Reagents for Protein Modification, 1984
The development of peptide chloromethyl ketones which serve as affinity labels for serine protease-like enzymes with “tryptic”-like specificity serves as a good example of the logical development of an active-site directed inhibitor. It was first established that trypsin preferentially hydrolyzed peptide bonds in which the carboxyl group was provided by a lysine or arginine residue.55 It was subsequently shown that various amides and guanidines would effectively bind to trypsin.7 Inagami then demonstrated that alkylation of the active site histidine with iodoacetamide occurred much more rapidly in the presence of a reagent (i.e., methyl guanidine) than in the absence of such a compound.56 These observations then led to the development of N-tosyl-l-lysine chloromethyl ketone (l-chloro-3-tosylamido-7-amino-2-heptanone, TLCK, TosLysCH2Cl) as an active-site directed reagent (affinity label) (Figures 18 to 21) for trypsin8 which was later shown to react with histidine residue 43 (His 57 in chymotrypsin numbering system) at the N-3 position.58 It is of interest to note that another compound, p-guanidinophenacyl bromide, which is also an analogue of a trypsin substrate (inhibitor) inactivates trypsin by modification of the active site serine residue (Ser-183)59 (see Figure 22).
Proteases as Catalysts in Protecting Group Chemistry
Willi Kullmann in Enzymatic Peptide Synthesis, 1987
An alternative α-COOH protecting group, the phenylhydrazide moiety, which is chemically related to the anilides, can also be introduced by papain catalysis.34 In contrast to the anilides however, the phenylhydrazides are readily and selectively removable by oxidizing agents such as ferric chloride or copper acetate.35 The preparation by papain-catalysis of a series of different Nα-acyl amino acid derivatives using Phenylhydrazine C-terminal protection has been reported by Milne and Stevens36 and Milne and Carpenter.37 Beyond that, this method has also been successfully applied to the synthesis of the enkephalins and chole-cystokinin-related peptides.38,39 With the exception of proline, the α-carboxylate phenylhydrazides of all codogenous Nα-protected amino acids have been selectively synthesized via papain catalysis by Čeřovský and Jošt.40 Although there were significant differences in reaction yields between the respective amino acid derivatives, this study demonstrated the facility of papain as an almost universal condensation reagent. In this work amino acids bearing benzyloxycarbonyl- and t-butyloxycarbonyl Nα-protector groups, respectively, were used; however, Nα-9-fluorenylmethyloxycarbonylamino acids did not react with phenylhydrazide in the presence of papain. In addition to papain, trypsin has also been used to catalyze the conversion of peptides to the corresponding peptide phenylhydrazides.41 Furthermore, trypsin will also catalyze the introduction of esters, hydrazides, and substituted hydrazides, such as Boc-NHNH2 and Z-NHNH2 into α-COOH groups.41,42
Urinary peptidomics in kidney disease and drug research
Published in Expert Opinion on Drug Discovery, 2018
Magdalena Krochmal, Joost P Schanstra, Harald Mischak
Assessment of endogenous, naturally occurring peptides (peptides present in vivo) is the primary focus of peptidomics technologies. In the course of years, researchers moved from focusing on single-peptide to the characterization of entire peptidomes. Peptidomics approaches typically do not involve enzymatic digestion, as it is in case of proteomics experiments; however, sample preparation remains complex, given the high granularity of information on peptide level [6]. Peptidomics methods are based on mass spectrometry (MS), typically preceded by a separation step and subsequent employment of electrospray ionization or matrix-assisted laser desorption ionization (MALDI). The high-resolution separation techniques, such as liquid chromatography or capillary electrophoresis (CE), further increase resolving power. Advantages of the techniques include fast analysis, low limits of detection, as well as excellent mass accuracy. Furthermore, by avoiding digestion, PTMs can very well be detected, but also interfere with identification (by changing mass, affecting fragmentation, and consequently identification). The workflow of CE-MS analysis of urine samples is illustrated in Figure 1.
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
Peptidomimetics are designed based on small protein-like chains or small molecules that mimic the behavior of a peptide and have regulated molecular properties, such as high stability or biological activity. The use of peptidomimetics is a very powerful strategy for designing small molecule-based drugs as enzyme inhibitors or receptor ligands [106]. These compounds mimic a natural peptide or a protein of the viruses and have the ability to interact with their biological targets and produce the same biological effects [107]. There are different types of changes to create peptidomimetics with improved drug properties, including local changes, such as the binding of nonstandard amino acids, and general changes, such as forming a circular end in polypeptide chains during a cyclization process. Cyclization is one of the most common strategies used to convert peptides into drugs and pharmacologically active agents [108].
In vitro and molecular docking studies on a novel Brevibacillus borstelensis NOB3 bioactive compounds as anticancer, anti-inflammatory, and antimicrobial activity
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Hend A. Hamedo, Aya A. Elkashef, Mohamed A. I. Mansour, Naglaa Elshafey
The agar-well diffusion method was used to assess the Brevibacillus borstelensis NOB3 extract’s antimicrobial properties [29]. For bacterial cultures, nutrient broth was used; for fungal cultures, a broth containing 1% peptone and 2% dextrose was utilized. 75 mL of the medium was poured into petri plates to create them, and the agar was allowed to set. Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 90,274), Candida albicans (ATCC 10,221), and Mucor reinelloids were the references microorganisms obtained from Ain Shams Hospital, and they served as the test’s target pathogens. A sterile cotton swab was used to disperse a freshly made microbial inoculum (1 mL) uniformly across the entire agar surface. The extract was then put into a well that had been created with a sterile cork borer (6 mm). After one hour at room temperature, petri plates were incubated at the proper conditions depending on the organism being examined. Parallel controls were carried out where the well was filled with extract. The plates were examined for zones of inhibition, and the outcomes were compared to those of the positive control using Gentamicin (30 g/mL).