My research is on Drug binding studies with human serum albumin, the main aim of our project is to study the pharmacokinetic, pharmacodynamic properties of HSA with different drug molecules which have medical significance.The study gives information which is helpfull for designing drugs for more efficient delivery to target organs for efficiant action.
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin comprises about half of the blood serum protein. It is soluble and monomeric.
The gene for albumin is located on chromosome 4 and mutations in this gene can result in various anomalous proteins. The human albumin gene is 16,961 nucleotides long from the putative 'cap' site to the first poly(A) addition site. It is split into 15 exons which are symmetrically placed within the 3 domains that are thought to have arisen by triplication of a single primordial domain.Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin.
The reference range for albumin concentrations in blood is 30 to 50 g/L. It has a serum half-life of approximately 20 days. It has a molecular mass of 67 kDa.
Functions of albumin
- Maintains oncotic pressure
- Transports thyroid hormones
- Transports other hormones, particularly ones that are fat soluble
- Transports fatty acids ("free" fatty acids) to the liver
- Transports unconjugated bilirubin
- Transports many drugs; serum albumin levels can affect the half-life of drugs
- Competitively binds calcium ions (Ca2+)
- Buffers pH
- Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is not a valid marker of nutritional status; rather, it is a marker in inflammatory states
- Prevents photodegradation of folic acid
Amino Acid Sequence
The approximate sequence of human serum albumin is:
MKWVTFISLL FLFSSAYSRG VFRRDAHKSE VAHRFKDLGE ENFKALVLIA FAQYLQQCPF EDHVKLVNEV TEFAKTCVAD ESAENCDKSL HTLFGDKLCT VATLRETYGE MADCCAKQEP ERNECFLQHK DDNPNLPRLV RPEVDVMCTA FHDNEETFLK KYLYEIARRH PYFYAPELLF FAKRYKAAFT ECCQAADKAA CLLPKLDELR DEGKASSAKQ RLKCASLQKF GERAFKAWAV ARLSQRFPKA EFAEVSKLVT DLTKVHTECC HGDLLECADD RADLAKYICE NQDSISSKLK ECCEKPLLEK SHCIAEVEND EMPADLPSLA ADFVESKDVC KNYAEAKDVF LGMFLYEYAR RHPDYSVVLL LRLAKTYETT LEKCCAAADP HECYAKVFDE FKPLVEEPQN LIKQNCELFE QLGEYKFQNA LLVRYTKKVP QVSTPTLVEV SRNLGKVGSK CCKHPEAKRM PCAEDYLSVV LNQLCVLHEK TPVSDRVTKC CTESLVNRRP CFSALEVDET YVPKEFNAET FTFHADICTL SEKERQIKKQ TALVELVKHK PKATKEQLKA VMDDFAAFVE KCCKADDKET CFAEEGKKLV AASQAALGL
The italicized ( indicated in red ) first 24 amino acids are signal and propeptide portions not observed in the transcribed, translated and transported protein but present in the gene. There are 609 amino acids in this sequence with only 585 amino acids in the final product observed in the blood.
Role of HSA in drug trasport,delivery.
Human serum albumin is a major extracellular protein with high affinity for a wide range of metabolites and drugs and its abundance is high in the blood plasma (40 mg ml21). The most important physiological roles of this protein are to bring such solutes into the bloodstream and deliver them to the target organs and to maintain the pH. In addition to its ordinary clinical applications such as hypovolemic shock treatment, many
investigators have attempted to utilize HSA as carrier to deliver various drugs to their specific target organs. HSA is a single nonglycosylated, 67 kDa polypeptide, which folds into a heart shaped protein with approximately 67% a-helical content. It is a globular protein composed of three structurally similar domains (I–III), each consisting of two subdomains (A and B) and stabilized by 17 disulfide bridges. The two primary binding sites (site I and site II) are hydrophobic cavities located in subdomains IIA and IIIA, respectively. Most compounds binds to these two sites with an affinity constant of 104 to 106 M21 . In addition, seven binding sites for fatty acids are localized in sub-domains IB, IIIA and IIIB, and on the sub-domain interfaces . HSA also has a high-affinity metal binding site at the N-terminus . There are many reports containing studies on HSA structure and its interactions with different ligands.
investigators have attempted to utilize HSA as carrier to deliver various drugs to their specific target organs. HSA is a single nonglycosylated, 67 kDa polypeptide, which folds into a heart shaped protein with approximately 67% a-helical content. It is a globular protein composed of three structurally similar domains (I–III), each consisting of two subdomains (A and B) and stabilized by 17 disulfide bridges. The two primary binding sites (site I and site II) are hydrophobic cavities located in subdomains IIA and IIIA, respectively. Most compounds binds to these two sites with an affinity constant of 104 to 106 M21 . In addition, seven binding sites for fatty acids are localized in sub-domains IB, IIIA and IIIB, and on the sub-domain interfaces . HSA also has a high-affinity metal binding site at the N-terminus . There are many reports containing studies on HSA structure and its interactions with different ligands.
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