enzymes

Question 1

Pro-drugs examples

Answer 1

E.g., enealarpil converted to enalaprilat (ACEI), codeine to morphine

Question 2

What structural aspect is used to classify Proteases

Answer 2

1133 members.

Subclassified based of AA in active site, e.g., aspartyl, cysteine, serin, metallo-, mixed

Question 3

Protease inhibitors examples

Answer 3

ACEIs

DPP4 inhibitors convert GLP-1 to an inactive product + dipeptide, for DM2 (e.g., sitagliptin, saxagliptin)

proteasome complex inhibitors(hydrolyses ubiquitin tagged proteins (e.g., thalidomide, bortezomib)

and HIV protease inhibitors (e.g., ritonavir, squinavir)

Question 4

Kinases examples and regions that can be bound

Answer 4

516 in humans

E.g., RTK, RSTK, etc… many are catalytic receptors.

Drugs may bind to ATP binding site, protein binding site, or an allosteric site.

Question 5

Kinase inhibitors examples

Answer 5

EGFR inhibitors to treat non-small cell lung cancer, and breast cancer (e.g., erlotinib, afatinib, lapatinib)

VEGFR inhibitors to treat renal cell carcinoma (e.g., axitinib)

Bcr-Abl inhibitors to treat chronic myelogenous leukaemia (e.g., imatinib, bosutinib)

B-Raf inhibitors to treat melanoma - gain of function mutation associated with melanomas (e.g., dabrafenib, vemurafenib)

Question 6

factors for drugs to target EC enzymes and examples

Answer 6

Drug can be charged and water soluble.

Neostigmine and physostigmine (AKA eserine) are AChE inhibitors for myasthenia gravis, where autoantibodies inactivate NMJ nAChRs.

Orlistat is a pancreatic lipase inhibitor to treat obesity. Reduces lipid absorption. Remaining lipids act as osmotic laxative, and cause steatorrhoea.

Acarbose is a alpha-glucosidase inhibitor to treat DM2.

Question 7

Factors for drugs to target IC enzymes and examples

Answer 7

Must be lipid soluble, and/or a transporter substrate.

Anastrozole is an aromatase inhibitor that prevents the formation of estrogen and estradiol which enhance the proliferation of hormone-sensitive breast cancer

5-fluorouracil treats colorectal or pancreatic cancer. it is a surrogate nucleobase. Also inhibits thymidylate synthase to stop cell proliferation.

Question 8

Suicide substrates binding mechanism and examples

Answer 8

They bind to the substrate site irreversibly, inhibiting the enzyme permanently.

Eflornithine irreversibly inhibits ornithine decarboxylase to treat sleeping sickness. Prevents nucleic acid replication and cell division in the parasite

Penicillins are also a suicide substrate for transpeptidases in bacteria to degrade the cell wall by inhibiting the cross-linking of peptidoglycans.

azidothymacin (AZT) is a retroviral for HIV. irreversibly inhibits viral reverse transcriptase to prevent the replication of HIV.