9. Draw the structure of the product that would form by the action of a PLP-requiring amino acid racemase on Drug A shown in the graphic below. HOOC NH₂ HẠNH CHÍNH: Drug A COOH Amino Acid Racemase Pyridoxal Phosphate
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- Which of these heterocyclic drugs is likely to be the least soluble in water? Use the Fsp³ parameter to decide. OH Tramadol Chemical Formula: C16H25NO2 YOUR OW Pantoprazole Torasemide Chemical Formula: C16H15F2N3O4S Chemical Formula: C16H20N4O3S Temazepam -OH Chemical Formula: C16H13CIN₂O2 Tioconazole Chemical Formula: C16H13C3N₂OS A. Tramadol B. Pantoprazole C. Torasemide D. Temazepam E. Toconazole4. Draw the ATIII binding pentasaccharide structure; indicate critical 3-0 sulfate, 6-0 sulfate and Glucuronic acid residue3. Solve the sequence of an oligopeptide 7 residues long which gave: Asp Leu Lys Met Phe Tyr The following facts were observed: a. Trypsin treatment had no apparent effect b. The PTH derivative from Edman degradation was c. Brief chymotrypsin treatment yielded several products including but not limited to a dipeptide and a tetrapeptide. The amino acid composition of the tetrapeptide was Leu, Lys, and Met. d. Cyanogen bromide treatment yielded a dipeptide, a tetrapeptide, and a free Lys.
- 3. Solve the sequence of an oligopeptide 7 residues long which gave: Asp Leu Lys Met Phe Tyr The following facts were observed: a. Trypsin treatment had no apparent effect b. The PTH derivative from Edman degradation was c. Brief chymotrypsin treatment yielded several products including but not limited to a dipeptide and a tetrapeptide. The amino acid composition of the tetrapeptide was Leu, Lys, and Met. d. Cyanogen bromide treatment yielded a dipeptide, a tetrapeptide, and a free Lys. Instructions Make use of the table below to determine the sequence of the mystery protein.2. To the right is a schematic diagram of His $7 the active site in the Michaelis complex of a-chy- motrypsin and a polypeptide substrate. Describe briefly the catalytic or structural roles of the residues listed below: но — Ser 195 (а) Ser195 AA,-C-ÇH-NH-C-ÇH -NH -AAn R R H H. 193 Gly Ser195 (b) His57 (c) NH groups of Gly193 and Ser195 (d) The most favorable side chain R for binding (e) Identify the scissile bond with an arrow, i.e., the bond in the peptide substrate that is cleaved as a result of the catalytic action of the enzyme. You can point to it on the diagram above.15. Write the metabolites of the following substrates due to phase Il reactions: a. b. R R C. R R NH NH LOH 3'-phosphoadenosine-5'-phosphosulfate Enzyme S-adenosylmethionine Enzyme Acetyl-SCOA
- 1. Gemtuzumab and Trastuzumab emtansine are two examples of mAb-drug conjugates (ADCS) where the thiol-containing drugs calicheamicin and DM1, respectively, are attached to the mAb's via the linkers shown below. SO, Na „SH Thiolhydrazide in Gemtuzumab Sulfo-SMCC in Trastuzumab emtansine (i) Show the chemistry involved in conjugating the drug (Calicheamicin-SH) to the antibody in Gemtuzumab and draw the target mAb-drug conjugate with a detailed linker region. Show the chemistry involved in conjugating the drug (DM1-SH) to the antibody in Trastuzumab and draw the target mAb-drug conjugate with a detailed linker (ii) region.explain why A liposome of 1;1 molar ratio of cholesterol to phospholipids will be the optimum combination for the highest concentration of drug entrapment’6. Cholestatic effects of pharmaceuticals present serious complications that often require restrictions in dose or termination of therapy. Give the potential mechanisms for cholestasis and one compound associated with each mechanism.
- 6. The Vmax and KM values for an unusual hexokinase found in Try- pansoma cruzi (the causative agent of Chagas disease) are shown in the presence and absence of a bisphonate inhibitor (structure shown). Without inhibitor With inhibitor Км (mM) 90 125 Vn max (umol min-1. mL-1) 0.30 0.12 ОН O=P-O- A bisphonate compound a. What type of inhibitor is bisphonate? b. The parasite hexokinase, unlike the mammalian enzyme, is not inhibited by glucose-6-phos- phate but is inhibited by pyrophosphate (PP;). Is this observation con- sistent with your answer to part a? c. Might bisphonate be a good candidate for a drug to treat the disease?15. Write the metabolites of the following substrates due to phase Il reactions: a. b, R R C. R R NH ΝΗ LOH 3'-phosphoadenosine-5'-phosphosulfate Enzyme S-adenosylmethionine Enzyme Acetyl-SCOADraw the structure of the following 1.Alanylaspartylglutamyltryrosin 2. Tetrapeptide