Molecular Recognition and Chemical Modification of Biopolymers — Two Main Components of Affinity Modification
Dmitri G. Knorre, Valentin V. Vlassov in Affinity Modification of Biopolymers, 1989
The ability of biopolymers in particular proteins to function as biologically active molecules is firmly connected with the ability to form definite spatial structures. The most detailed knowledge of coordinates of all atoms of biopolymers is based on the results of X-ray crystallography. One of the most general results of these data is the elucidation of two main levels of spatial structure of biopolymers. The first, more primitive level is periodical secondary structure. For proteins, the main regular elements of the structure are α-helixes and β sheets which are presented in Figures 4 and 5. The formation of these structures is an inherent property of the polypeptide chain. Side-chain radicals distributed along the chain may favor or hinder the formation of these structures. Therefore, the primary structure of a polypeptide (the sequence of amino acid residues) predetermines the preferential conformation of any fragment of polypeptide chain as well as the breaks of these periodic elements. The interaction between side-chain radicals forming a helixes or β sheets results in the formation of a unique three-dimensional tertiary structure with a definite topology of the periodical fragments and joining sequences.
Conditioning of Hair
Dale H. Johnson in Hair and Hair Care, 2018
b. Proteins. Proteins serve many diverse biological functions acting as catalysts in enzymes, structural elements in bone collagen and hair keratin, nutrient storehouses in milk casein and egg ovalbumin, and many more. Proteins are made up of one or more polypeptide chains which in turn are made up of many alpha-amino acid residues linked together by a peptide bond. There are 20 different alpha-amino acids commonly found in proteins (42), listed in Table 2. All of these amino acids, except for proline, contain a free carboxyl group and a free unsubstituted amino group on the alpha-carbon. The amino acids differ from one another by their side chain R groups. Many amino acid residues are arranged in complex specific sequences to form proteins which range in molecular weight from about 5000 to over 1 million.
Translation and Post-Translational Modifications During Aging
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
The genetic information encoded in DNA becomes functionally meaningful only when it is accurately transcribed and translated into RNA and proteins, respectively. Whereas two types of RNA, transfer (t) RNA and ribosomal (r) RNA, are themselves functional molecules, the genetic information transcribed into the third RNA, messenger (m) RNA, has to be translated from a language of nucleic acids into a language of amino acids in order to produce proteins, which are the functional products of the genes. It has been estimated that in a human cell there are about 80,000 genes per haploid genome, of which about 22,000 are housekeeping genes and the rest are tissue specific.1 Furthermore, in order to become a functional protein, a newly synthesized polypeptide chain has to undergo a wide variety of posttranslational modifications that determine its activity, stability, specificity, and transportability.
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
Transferrins are iron-binding proteins with antiviral activity. The most well-known transferrin is lactoferrin (LF), which is a multifunctional 80-kDa glycoprotein and is widely available in various secretory fluids. LF, first discovered in cow’s milk, is evolutionarily highly conserved and is found in humans, mice, and pigs. Its structure consists of a polypeptide chain that has a positively charged N-terminal region. The LF chain has two circular loops connected to three spiral α-helixes, each of which has an iron-binding site. There is a strong connection between two loops when iron binds (the holo-form), which makes LF resistant to proteolysis [40]. Reports have indicated that bovine lactoferrin is a potent inhibitor of a broad number of viruses and has higher antiviral effects than human lactoferrin. Lactoferrin specifically binds to the subunit A2 of the hemagglutinin and inhibits influenza virus infection and related hemagglutination [63]. Lactoferrin has been shown to inhibit infection by binding to adenovirus III and IIIa structural polypeptides targets [64]. The inhibitory effect of LF on DENV [65], Marek’s Disease Virus (MDV) [66], and HCV [67] has been investigated. Recent studies showed that LF can interfere with some of the receptors involved in SARS-CoV-2 pathogenesis and also prevents the entering of the virus via ACE2 to host cells [68]. Therefore, LF may contribute to the prevention and treatment of COVID-19 [68].
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
Ribosomes are ribonucleoprotein complexes discovered by Palade and Porter in 1954 as small round bodies associated with the endoplasmic reticulum (ER), as observed using an electronic microscope [1]. It is well known that genetic information is stored in deoxyribonucleic acid (DNA) molecules, and by the highly regulated mechanism of transcription, genes, as particular segments of DNA, are copied into mRNA (ribonucleic acid) by the RNA polymerase enzyme. Ribosome macromolecules catalyze the translation of information from mRNAs into functional polypeptide chains. Ribosomes consist of large and small subunits. Eukaryotic ribosome consists of a smaller 40S subunit and a large 60S subunit. The smaller 40S subunit consists of 18S ribosomal RNA (rRNA) and 33 ribosomal protein small (RPS) subunits, whereas the 60S subunit contains 28S, 5S, and 5.8S rRNA and 47 ribosomal protein large (RPL) [2,3].
MRGPRX2 activation as a rapid, high-throughput mechanistic-based approach for detecting peptide-mediated human mast cell degranulation liabilities
Published in Journal of Immunotoxicology, 2020
Marc A. Lafleur, Jonathan Werner, Madeline Fort, Edward K. Lobenhofer, Mercedesz Balazs, Ana Goyos
Mast cells express multiple receptors that recognize a wide spectrum of activating ligands. Some of these include IgEs when bound to fragment crystallizable epsilon receptor I (FcεRI) (Stone et al. 2010) and cross-linked by allergens or IgGs bound to FcγRI (Woolhiser et al. 2004), complement proteins (such as C3a and C5a) binding to their cognate receptors (Zwirner et al. 1998; Woolhiser et al. 2004; Ali 2010), pathogen products binding to toll-like receptors (Akira et al. 2001; Tkaczyk et al. 2006), and a diverse range of basic ligands binding to the human Mas-related G protein-coupled receptor X2 (MRGPRX2) (McNeil et al. 2015; Subramanian et al. 2016; Grimes et al. 2019). Basic ligands include endogenous peptides (e.g. Substance P and somatostatin) (Church et al. 1991), venoms (e.g. mastoparan and melittin) (Hartman et al. 1991; Mendes et al. 2005), and peptide-based therapeutics (e.g. octreotide and cetrorelix) (Broqua et al. 2002; McNeil et al. 2015). Peptides are generally defined as polypeptide chains having < 50 amino acids (Sato et al. 2006). Life-threatening anaphylactoid reactions are thus a significant potential safety liability for peptide modalities in drug development (Polk 1991; Verschraegen et al. 2003; Grimes et al. 2019; Zhan et al. 2019). Because the nature of peptides that bind MRGPRX2 are quite diverse and activation cannot be predicted from sequence similarity alone (Lansu et al. 2017), rapid, high-throughput screening tools for MCD hazard identification are consequently highly valuable as part of an early MCD liability detection strategy for peptide-based therapeutics in drug development.