BioTherapi: Bioinformatics for Therapeutic Peptides and Proteins

In Post genomic era the number of protein sequence in databases increases exponentially. In order to understand their therapeutic importance and in future for synthesizing peptide/protein for medicinal importance, it is mandatory to having the knowledge of exisitng peptide/protein of therapeutic value. At present their is no single platform that provide this kind of information. Thus as open source project and providing maximum information this platform developed.
This include all the relevant information about the use of Peptides/Proteins in drug and synthesis of new peptides. It also cover problems, in their formulation, synthesis and delivery process.


Important Terms

• Pegylation: PEGylation is the process of covalent attachment of Polyethylene glycol polymer chains to another molecule, normally a drug or therapeutic protein.PEGylation, by increasing the molecular weight of a molecule, can impart several significant pharmacological advantages over the unmodified form, such as:
  * Improved drug solubility
  * Reduced dosage frequency, without diminished efficacy with potentially reduced toxicity
  * Extended circulating life
  * Increased drug stability
  * Enhanced protection from proteolytic degradation
  
• Methylation: In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence. Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylated arginine) or one on both nitrogens (symmetric dimethylated arginine) by peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by lysine methyltransferases. Protein methylation has been most well studied in the histones. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases. Histones that are methylated on certain residues can act epigenetically to repress or activate gene expression. Protein methylation is one type of post-translational modification.
• Glycosylation: Glycosylation is the enzymatic process that links saccharides to produce glycans, attached to proteins, lipids, or other organic molecules.Glycans serve a variety of structural and functional roles in membrane and secreted proteins.The majority of proteins synthesized in the rough ER undergo glycosylation. It is an enzyme-directed site-specific process, as opposed to the non-enzymatic chemical reaction of glycation.
  * N-linked glycans attached to a nitrogen of asparagine or arginine side chains
  * O-linked glycans attached to the hydroxy oxygen of serine, threonine, tyrosine, hydroxylysine, or hydroxyproline side chains, or to oxygens on lipids such as ceramide
  * phospho-glycans linked through the phosphate of a phospho-serine
  * C-linked glycans, a rare form of glycosylation where a sugar is added to a carbon on a tryptophan side chain
  * glypiation, which is the addition of a GPI anchor that links proteins to lipids through glycan linkages.
  
• Lipidization: Lipidization is a chemical modification that can increase the lipophilicity of a polypeptide molecule.
• Cationization: Cationization of drug products and carriers involves a direct modification or attachment of conveying or accompanying components, either of which cause a charge modification. Cationization of macromolecules such as proteins and nucleotides and paniculate drug carriers generally enhances their cellular uptake by endocytosis. The most common use of cationization today is in gene delivery. This is undertaken by either employing cationic polymers or entraping nucleotides in cationic carriers such as cationic liposomes. Cationized delivery systems are also used to overcome biological barriers and are suggested for drug targeting, in a nonspecific manner, to a variety of body organs, including brain, eyes, nose, and inflamed intestinal epithelium. Protein cationization is also suggested both for tumor immunotherapy and as a diagnostic tool in cancer therapy. Cationization has proven itself to be a straightforward tool for targeting to cells, tissues, and selected organs.
• Backbone and termini modification:
• Structural rigidification:
• Cyclization:
• Vector-mediated transport:
• Polymer conjugation and encapsulation:
• Bioavailability: In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%.[1] However, when a medication is administered via other routes (such as orally), its bioavailability decreases (due to incomplete absorption and first-pass metabolism) or may vary from patient to patient (due to inter-individual variation). Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.It is denoted by the letter F.
  
• Metabolic stability:
• Improved pharmacokinetic profiles:
• Peptidomimetics:
• Peptoid:
• Beta-peptide:
• Mimotope:
• Opioid:
• Phage display peptide library:
• Peptide Library Synthesis:
• Codon-shuffling:
• Cell-free expression system:
• Enzymatic Synthesis:
• Pseudo Peptide Bonds:
• t-Boc/Bzl:
• Fmoc/-t-bu:
• Biodistribution :
• Aqueous Solubility:
• Lipophilicity:
• H-bond formation :
• Proteolytic Enzymes (peptidase) :
• Aminopeptidase :
• Carboxypeptidase C:
• Esterase:
• Half-life of peotides:
• Blood Brain Barrier (BBB):
• Cyclic Peptides:
• Pseudo-peptides:
• Chemical Optimization of Peptides:
• Minimum Active Sequence:
• Alanine scanning (Ala-scan):
• D-scanning (D-scan):