Rules of the Day
4-24-2025
Click here for a copy of the lectures notes I wrote in class
Click here for a copy of the handout I used in class today
Click here for a copy of the songs we sang today.
1. Fentanyl is more dangerous than narcotics isolated from plants like heroin and cocaine because fentanyl is too easy to make and it is so much more potent, you do not need to transport very much material (it is too easy to hide).
2. Fentanyl binds to the mu-opioid receptor to provide a sense of euphoria (it is therefore a mu opioid agonist), but fentanyl also leads to release of A LOT of dopamine in many people, explaining why it is so addictive.
3. THERE IS NO SUCH THING AS BLACK MARKET ADDERRAL OR XANAX, THEY ARE ALL FAKE. THEY ONLY CONTAIN METHAMPHETAMINE AND FENTANYL. THESE FAKE PHARMACEUTICALS CAN KILL YOU! THEY HAVE KILLED OTHER LONGHORNS INCLUDING JAKE ELLINGER! 2 Milligrams of fentanyl will kill you. It is 150 times more potent than heroin.
4. Narcan (naloxone) is an antagonist of the mu-opioid receptor, it binds to the receptor but does not activate it or release dopamine. It binds to tightly that it can occupy all of the mu opioid binding sites and rescue a person who has OD'd on fentanyl and stopped breathing, provided it is given as a nasal spray soon enough.
5. Each of you should carry some Narcan, you can get it at the PCL circulation desk, free of charge. You just might save a life!
6. The AIDS virus is a single stranded RNA retrovirus meaning a virus particle is a single strand of RNA surrounded by virus proteins. Once inside host cells, the RNA is reverse transcribed to DNA, that then integrates into the genomes of host cells. After an unknown signal the DNA becomes active and is transcribed to long polyprotein mRNAs. A polyprotein transcript is produced from the mRNA called GAG-POL that is cleaved into functional proteins by the AIDS protease.
7. Enzymes catalyze reactions by 1) having acids, bases and nucleophiles in the active site in exactly the right places in 3-dimensions AND 2) by stabilizing transition state structures.
8. The AIDS protease is an aspartyl protease that uses two carboxylic acid groups and a water molecule to hydrolyze an amide bond at neutral pH and at room temperature.
9. Drugs are designed to interfere with the biochemical steps that are unique to the virus, in particular the reverse transcriptase (RNA to DNA) and AIDS protease steps (cleavage of GAG-POL polyprotein into individual virus proteins).
10. The AIDS protease inhibitors are designed to resemble the key tetrahedral intermediateof the amide hydrolysis reaction while maximizing complementary contacts within the active site.
11. Because the reverse transcriptase step makes a significant number of errors, the HIV genome mutates quickly and the target enzymes (reverse transcriptase and AIDS protease) can become resistant to any one drug, so "cocktails" of several drugs are used to counteract resistance.
12. I believe that developing a treatment for AIDS in about a decade stands alongside getting to the moon as one of this countries great technical achievements. The core ideas behind creating the drug are based on 1) understanding the mechanism of the enzyme reaction to be inhibited, 2) design possible drugs that bind only to the disease target, 3) synthesize then test thousands of derivatives to find the precious few that can be taken as pills and cause minimum side effects, make sure they are safe and effective, then synthesize them in large amounts in pure form, batch after batch.
You may be interested in the following publications, the ones I mentioned.
HIV drug development based on enzyme target mechanisms
Another HIV protease inhibitor review article
Opioid Receptor Structure with Bound Fentanyl
13. The COVID pandemic was contained using amazing new technologies from space-age lipid nanoparticles to nucleic acid analogs to protease inhibitors that make covalent bonds to the target enzyme. We will discuss the incredible breakthroughs that led to the successful vaccines and antivirals against COVID! Click here to see an explanation of the Delta and Omicron variants.
15. "The only real valuable thing is intuition"...........Albert Einstein
16. "Understanding Where Electrons Are and knowing how to apply the Golden Rules of Chemistry will make Organic Chemistry class as simple as possible, and will give you Organic Chemistry intuition"............Fortune Cookie Saying
17. "Organic is really hard if you try to memorize it instead of trying to learn and understand it"............The Organic Vampire Monkey
Understand and learn. Do not only memorize!
18. The Golden Rules of Organic Chemistry explain most of what we will learn about organic chemistry.
19. The POINT of organic chemistry is synthesis; making complex molecules from simpler ones.
20. We have tried to prepare you for your later biochemistry courses by emphasizing key molecular principles that are important for the properties and reactions of the molecules of life.
21. I have been honored to be on this Organic Chemistry journey of discovery with you. You are an amazing class. Best of luck on the final! Please say "Where are the electrons?" whenever you see me on campus!
Homework:
There are no quizzes, readings or homeworks for the rest of the semester! When you are ready you can work on a practice homework that will help you prepare for the final. You will not turn it in. Click here for the questions and click here for the answers.
