Protein therapeutics.

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Presentation transcript:

Protein therapeutics

What are therapeutic proteins? These are the proteins that has an effect of healing or use inside our body, e.g: Nutrition: the use of albumin (its the same in all human beings) Globulins: the example is gamma globulin that your defenses against infectious diseases (gamma globulin is a mixture of antibodies) Synthetic proteins: antibodies against inflammatory components, or against tumor components

Protein structures for therapeutics :

What is inside??? Copyright 2004 by Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter.

Attractive features : Why Protein against small drug molecules? The diversity of functional groups in protein : free thiols on cystein residue & amine on the N-terminus or on lysin residue Scope for functionalization. Highly specific function less chance of being mimicked by simple chemical compounds. High specificity in action less potential for protein to interfere with normal biological processes. The body naturally produces many of the proteins that are used as therapeutics, & hence are often well tolerated and are less likely to elicit immune responses.

The evolution of Protein therapeutics : 1953 First accurate model of DNA suggested 1982 Human insulin, created using recombinant DNA technology 1986 Interferon alfa and muromonab-CD3 approved 1993 CBER's Office of Therapeutics Research and Review (OTRR) formed 1997 First whole chimeric antibody, rituximab, and first humanized antibody, daclizumab, approved 2002 Market for biotechnology products represents approximately $30 billion of $400 billion in yearly worldwide pharmaceutical sales 2006 An inhaled form of insulin (Exubera) approved, expanding protein products into a new dosage form.

Classification of Protein therapeutics Group I: protein therapeutics with enzymatic or regulatory activity Ia: Replacing a protein that is deficient or abnormal Ib: Augmenting an existing pathway Ic: Providing a novel function or activity Group II : protein therapeutics with special targeting activity IIa: Interfering with a molecule or organism IIb: Delivering other compounds or proteins Group III : protein vaccines IIIa: Protecting against a deleterious foreign agent. IIIb: Treating an autoimmune disease. IIIc: Treating cancer. Group IV : protein diagnostics

Protein therapeutics replacing a protein that is deficient or abnormal (Group Ia)

Protein therapeutics augmenting an existing pathway (Group Ib)

Protein therapeutics providing a novel function or activity(Group Ic)

Protein therapeutics that interfere with a molecule or organism (Group II a)

Protein therapeutics that deliver other compounds or proteins (Group II b)

Protein vaccines (Group III )

Protein diagnostics (Group IV )

Intracellular protein delivery system : Amphipatheic peptide carrier & Protein cargos Covalent modification of proteins with a peptide sequence that shows the capability to translocate membrane rapidly Modification involves 1> direct expression of recombinant fusion protein from a vector containing DNA sequence 2> protein or chemical conjugation to the protein through such as disulfide bond linkage To protect protein from protease degradation & strategy to improve delivery efficiency noncovalent encapsulation with different cargos with synthetic peptide.

Development of peptide based biomaterial for delivery : Why peptide? 1> Easy to synthesize 2> easy charecterization 3> less toxic & has higher immunogenicity 4> Due to its amphipathic character of peptides can associate rapidly with protein cargos in solution, possibly through noncovalent hydrophobic interaction

Amphipathic peptides involved in intracellular delivery of proteins/peptides

Targetted delivery : Protein polymer conjugate Most commonly employed polymer : Polyethylene glycol(PEG) & Poly(N-isopropylacrylamide) (PNIPAM) These polymers that alter their solubility or propensity for self-assembly when exposed to changes in pH or temperature allow their responsive nature to be conferred to the protein to which they are attached. Functionalizable with active esters & hence can be conjugated with protein.