اجوبة د كريمة - Lecture notes 1 PDF

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*What is unique about glycine compared with other naturally-occurring amino acids? 2) Glycine is the only amino acid with no side chain and is the only naturally occurring amino acid that is not asymmetric. *Identify the intermolecular/intramolecular interactions that are possible for the side chains of the following amino acids; serine, phenylalanine, glycine, lysine, aspartic acid, and aspartate.

*The chains of several cell membrane-bound proteins wind back and forth through the cell membrane, such that some parts of the protein structure are extracellular, some parts are intracellular, and some parts lie within the cell membrane. How might the primary structure of a protein help in distinguishing the portions of the protein embedded within the cell membrane from those that are not? 4) In the primary structure of the protein, a sequence of amino acids with hydrophobic side chains may indicate a transmembrane (TM) region (i.e it is located within the cell membrane as shown below) This is because hydrophobic side chains will interact more favourably with the fatty cell membrane than with the aqueous environments on either side of the cell membrane. Regions of the protein that are made up predominantly of polar side chains are almost certainly located intracellularly or extracellularly. However, it would be wrong to conclude that all amino acids with hydrophobic side chains are located in transmembrane regions and that all amino acids with polar side chains are located intracellularly or extracellularly. *The tertiary structure of many enzymes is significantly altered by the phosphorylation of serine, threonine, or tyrosine residues. Identify the functional groups that are involved in these phosphorylations and suggest why phosphorylation affects tertiary structure.

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*Explain the distinction between a binding site and a binding region. 1) A binding site is a hollow or cleft on the surface of a receptor protein into which a chemical messenger can fit and bind. A binding region is a specific region of that binding site, which is important in the binding process. It may contain a functional group capable of forming a specific bonding interaction with a functional group present on the guest molecule or ligand. Alternatively, it may be a hydrophobic region that can form van der Waals interactions with a hydrophobic region of the ligand. *Consider the structures of the neurotransmitters shown in Fig. 4.3 and suggest what type of binding interactions could be involved in binding them to a receptor binding site. Identify possible amino acids in the binding site which could take part in each of these binding interactions. 2) The possible binding interactions for the functional groups in each molecule are shown as HBD (hydrogen bond donor), HBA (hydrogen bond acceptor), ionic and vdw (van der Waals interactions). It should also be noted that van der Waals interactions involving alkyl groups or alkyl chains are possible. The following amino acids have side chains which could interact by hydrogen bonding: Ser, Thr, Tyr, Asn, Gln The following amino acids have side chains which could interact by ionic interactions: Asp, Glu, His, Lys, Arg The following amino acids have aromatic or heteroaromatic groups in their side chains which could interact by van der Waals interactions; Phe, Tyr, Try The following amino acids contain alkyl side chains which could interact by van der Waals interactions; Val, Leu. Ile. Met, Pro 2

In addition, the peptide links between amino acids in the binding site can interact with ligands by hydrogen bonding

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*There are two main types of adrenergic receptor: the α and β−adrenoceptors. Noradrenaline shows slight selectivity for the α-receptor, whereas isoprenaline shows selectivity for the β-adrenoceptor. Adrenaline shows no selectivity and binds equally well to both the α- and β-adrenoceptors. Suggest an explanation for these differences in selectivity.

*Suggest why the transmembrane regions of many membrane-bound proteins are α-helices.

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*Salbutamol is an anti-asthmatic agent that acts as an adrenergic agonist. Do you think it is likely to show any selectivity between the α- or β-adrenoceptors? Explain your answer. 3) This question is related to question 4 above. Larger and bulkier N-alkyl groups result in selectivity for the -receptors (see also section 23.10.3

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*Propranolol is an adrenergic antagonist. Compare the structure of propranolol with noradrenaline and identify which features are similar in both molecules. Suggest why this molecule might act as an antagonist rather than an agonist, and whether it might show any selectivity between the different types of adrenergic receptor.

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you were asked to design drugs that acted as selective antagonists of the dopamine receptor, what structures might you consider synthesizing?

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*Tamoxifen acts as an antagonist for the estrogen receptor. Suggest how it might bind to the receptor in order to do this.

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*The tamoxifen metabolite shown in Question 6 acts as an estrogen agonist rather than an antagonist. Why?

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