An Overview of Protease Inhibitors
Se-Kwon Kim in Marine Biochemistry, 2023
Proteases are seen in prokaryotes, fungi and animals and are very necessary for their survival. Proteases are enzymes that help to break down proteins in a method known as proteolysis. Such enzymes are present in a wide range of biological activities, from small protein digestion to extremely controlled cascades. Protease, like hormones, antibodies, and other enzymes, shows a vital physiological part in determining the life span of other proteins. In the physiology of organisms, this is one of the profligated “switching on” and “switching off” regulating systems. Proteases are secreted by a variety of bacteria to break the protein–peptide link into simple small monomers. As a result of multiple clinical trials suggesting their benefits in cancer studies include inflammations, immune regulations and blood flow control, their usage in medicine is garnering more and more attention. Many parasites are involved in pathogenesis, which includes parasite relocation through the host tissue barrier, hemoglobin and blood protein breakdown, immunological invasions, and inflammatory activation. Proteases thus show a decisive part in pathogenesis. Wild action, on the other hand, has negative consequences in the human body. These enzymes found within cancer cells have the ability to break other strong cell wall and membrane, allowing them to spread and grow into additional cell organ and part of the body, resulting in spread from one site to another (Figure 19.1).
Gold Nanomaterials at Work in Biomedicine *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
Proteases represent a major class of enzymes that catalyze the hydrolysis of peptide bonds to break down proteins into smaller pieces in a process known as proteolysis [407]. To this end, protein-stabilized fluorescent Au clusters can serve as probes for the detection of proteases. In the presence of proteases, the protein shell around each Au cluster will be broken down and the photoluminescence will be effectively quenched by the O2 from ambient air (Fig. 5.28A,B). By simply changing the protein substrates surrounding the Au clusters, this assay could be easily adapted for the detection of different proteases. With BSA-stabilized fluorescent Au clusters, the LOD for proteinase K reached 1 ng mL−1. Based on the selective interactions with ligands, many small molecules and heavy metal ions can also be detected through the principle of quenching photoluminescence from the Au clusters [415, 417].
Marine Algal Secondary Metabolites Are a Potential Pharmaceutical Resource for Human Society Developments
Se-Kwon Kim in Marine Biochemistry, 2023
Proteases enzymes, commonly known as biological catalysts, are responsible for a wide range of biochemical processes. They’ve been used in a variety of fields, especially therapeutics. The properties of molecules produced from the marine differ from those of their terrestrial counterparts. Marine microbes (epibionts and endosymbionts), which are abundant in unique environments, produce a plethora of medically and industrially essential molecules. These microbes secrete enzymes with specific characteristics like pH, metal, heat and cryo-tolerance and so on. Proteases are enzymes that break down lengthy chains of proteins into smaller fragments. Endopeptidases and exopeptidases are the two large families of proteases depending on their method of action. Exopeptidases degrade terminal amino acid positions attached to polypeptide chains, while endopeptidases catalyze the breakdown of peptide bonds in the middle portion of polypeptide chains. A further way of classifying proteases is by their optimum pH, which might be neutral, acidic, or alkaline. In terms of the active centers involved, enzymes can be classed as cysteine proteases, metalloproteases, serine proteases and aspartyl proteases.
Influences of Aflatoxin B1 on main intestinal bacteria communities and enzyme activities in mice
Published in Toxin Reviews, 2019
Lu He, Yawei Liu, Yanfang Guo, Nenqun Xiao, Zhoujin Tan
Amylase and protease are secreted by the intestinal tract while cellulase and xylanase are secreted by intestinal microorganisms. They are closely related to digestion and absorption as well as growth and development. The results of this study essentially supported the hypothesis that enzyme activity of the AFB1 groups presented a strengthening trend after intragastric administration of AFB1 solution. AFB1 solution could inhibit the damage on the organism and promote the activity of some digestive enzymes at low concentration. Meanwhile, the inhibiting effect on beneficial bacteria is not obvious, which can be used to explain the little changes in general situation of the mice and the overlook of carcinogenicity, teratogenicity, and mutagenicity. In addition, proteases are the catalysts that hydrolyze proteins into amino acids and enzymatic degradation of proteins is an important part of life, especially in digestion, immunity, and complement system. The results showed that the protease activity reduced as the increasing concentration of AFB1, which may be related to acute poisoning induced by AFB1 with high concentration.
Inhibition by components of Glycyrrhiza uralensis of 3CLpro and HCoV-OC43 proliferation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Jang Hoon Kim, Yea-In Park, Mok Hur, Woo Tae Park, Youn-Ho Moon, Yun-Chan Huh, Tae IL Kim, Min Hye Kang, Jong Seong Kang, Chong Woon Cho, Junsoo Park
SARS-CoV-2, of the Coronaviridae, is a positive-sense single-stranded RNA virus with a genome of ∼30,000 nucleotides and ∼ 89.1% similarity to SARS-CoV.10 After entering the cell, the virus releases RNA, which is then translated into two polyproteins (pp1a and pp1ab).11 These have two cysteine proteases, the papain-like protease (PLpro) and the chymotrypsin-like protease (3CLpro).11 Especially, the latter is one of the most representative target enzymes for the development of SARS-CoV-2 inhibitors.12 Polyproteins are cleaved into non-structure proteins by 3CLpro, which are key factors in virus propagation.13,14 Thus, 3CLpro is a target for the development of therapeutics.15
Antibody prodrugs for cancer
Published in Expert Opinion on Biological Therapy, 2020
W. Michael Kavanaugh
The second step is identification of a suitable protease substrate. To accomplish this, the proteases activated in the tumor microenvironment need to be identified, as do specific substrate sequences that are cleaved efficiently by those proteases when used in the context of a masked antibody. The tumor biology of numerous candidate proteases has been described in detail in the literature [6,7], and substrate sequences that can be cleaved by some of these proteases have been reported, although most are not specific and/or have suboptimal cleavage kinetics for this purpose. For example, substrates for matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9 are attractive candidates, because both their tumor biology and their substrate preferences are well described in the literature [13]. Substrates for tumor-associated serine proteases and other proteases have also been used [12].