Answers to Chapter 4 (in-text & asterisked problems)

Transcription

1 Introduction to ioganic hemistry and hemical iology 1 nswers to hapter 4 (intext & asterisked problems) nswer 41 The bulky tertbutyl group has a strong equatial preference, the following two confmations will be predominant The anti isomer cannot hydrolyze through neighbing group participation; the syn isomer can hydrolyze through neighbing group participation 3 P anti 3 P syn Introduction to ioganic hemistry and hemical iology 4096 nswer 42 There are two plausible mechanisms that avoid expulsion of an anionic 2 group Without some mechanistic data, you cannot predict which is the most likely Ō nswer 43 3' U U UU 5' 5' U 3' U 3' U U 5' UU 5' 3' stem loops Introduction to ioganic hemistry and hemical iology 4098 "kissing complex"

2 2 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 nswer 44 The following figure shows the minimum freeenergy structure from fold and eneee and the secondlowest energy structure from Mfold (the lowestenergy structure from Mfold did not match) UU U U 3' U U U U 5' U U U U U U U U nswer 45 four types of base pairs T,,, T 5' 3' four types of unpaired bases,,, T twelve types of mismatches,,,,, T,,, T, T, T, T T Total possibilities = = = 50,331,648 Introduction to ioganic hemistry and hemical iology 4100 nswer

3 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 3 nswer 47 ua yt template strand de Thy P Ura de P 3' Mg leaving group P P P yt ua ua yt 5' template strand de Thy P Pol Ura de P Mg 3' yt ua Mg P + P P ua yt 5' template strand de Thy P Ura de P yt ua Mg P 3' P P nswer 48 Triphosphates are highly susceptible to nucleophilic attack, particularly in the presence of Mg 2+ ions (not shown) The 2ʹhydroxyl group of a 3ʹnucleotidyl triphosphate would cyclize to give an unstable cyclic 2ʹ,3ʹphosphate yt P P P P P P Introduction to ioganic hemistry and hemical iology 4103 yt nswer 49 There are two possible hybrid pairs the Dbinding domain MS2 and the activation domain iron regulaty protein (as shown) Dbinding domain iron regulaty protein and activation domain MS2 (not shown) L4 Dbinding domains library MS2 viral coat protein iron regulaty protein transcription

4 4 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 nswer 410 nswer 411 The two lone pairs around the sulfur of the thioether are diastereotopic, as shown in the following structure The enzyme is selective f one of these lone pairs, generating the diastereomer of SM with a configurationally stable S configuration at sulfur The reaction with methyl iodide reacts with both lone pairs at approximately equal rates, leading to a mixture of and S sulfonium ions The natural S diastereomer of SM is a good substrate f methyltransferases, whereas the diastereomer is not SM (S)configuration S 2 3 S nswer 412 P lariat this P bond is cleaved by exposure to base n P de P Introduction to ioganic hemistry and hemical iology 4107 The phosphate indicated with the arrow still has an adjacent 2ʹ group, whereas the other two phosphate diesters lack the adjacent 2ʹ group This 2ʹ group can play a key role in mediating cleavage, as discussed earlier in the chapter

5 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 5 nswer 413 5'TTTTTTTTTTTTTTTTTTTTTTTT3' transcription sense 5'UUU UUUUUUUU U U U 3'UUUUUUUUUU antisense nswer P Introduction to ioganic hemistry and hemical iology 4109 nswer 415 Watson rick base pair ua ManQ Introduction to ioganic hemistry and hemical iology 4110 nswer 416 T T TT T TT TT U U UU U UU UU Met ly rg rg Pro la rg ys Tyr rg Tyr ys Lys sn (The threeletter abbreviations used here crespond to the first three letters of the amino acid, with the exception of asparagine and glutamine, which are abbreviated sn and ln to avoid confusion with aspartic acid and glutamic acid, respectively) nswer 417 yt 5' T T T T3' la lu Thr la sp la ly la la Pro la Val Ura Introduction to ioganic hemistry and hemical iology P 2450 So the number of possiple hexapeptides coded by these sequences is 2 6 = 64 wobble base pair

6 6 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 nswer 418 The Zn 2+ ion acts a Lewis acid, codinating to both the fmamide carbonyl and the hydroxide nucleophile The Zn 2+ ion activates the carbonyl group toward attack and brings the hydroxide nucleophile into proximity with the carbonyl carbon peptide peptide defmylase active actinoin defmylase active S site Zn site Zn ~ hydroxide anion Introduction to ioganic hemistry and hemical iology 4112 nswer 419 protein/peptide 2 Introduction to ioganic hemistry and hemical iology 4113 The enzyme lowers the entropic barrier by bringing the reactive carbon of D into close proximity with the diphthamide residue arbocation fmation is the ratedetermining step in an S 1 reaction The enzyme probably lowers the enthalpic barrier to ionization by stabilizing the oxocarbenium ion nswer 420 ecause chlamphenicol disrupts all protein translation, chlamphenicol will prevent the cells from expressing the plasmidencoded protein (chlamphenicol acetyl transferase) that confers resistance llowing the cells to grow befe exposure to chlamphenicol ensures an adequate supply of the proteins that confer resistance nswer 421 umber of 50mer s = 4 50 = Molecular mass of a 50mer D = g mol 1 = 15,250 g mol g 1 mol/15,250 g molecules mol 1 = / = (!) *nswer 422 3ʹTTTTT5ʹ 5ʹUU3ʹ 3ʹTTT5ʹ 5ʹU3ʹ nswer D + Me EF2 oxocarbenium ion + Me * 5' 3'

7 Introduction to ioganic hemistry and hemical iology nswers to hapter 4 7 nswer 424 * a P 1 M a a P a + * a P 1 M a a + a P *nswer 425 U U U ribozyme ribozyme U 5' U3' 5' 3' 3'UU5' 3'UU5' substrate substrate Introduction to ioganic hemistry and hemical iology 4116 *nswer 428 ote that the presence of start and stop codons confirms that the reading frame is crect ESSI X69154; lycine max ED401 m 1 gaauuccgcu aaaccaaucu aucaaguccu gauuaaucug gugagcu UUUUU 61 U UUUU UUagaag cuuggagaga aaggggugug agaggagagg 121 gugcucacuc cucacacucc cucacuuaaa acaguuuguu uuggcuuagc uuuggcuucu 181 cugaucaaca agggaugugu ucuaacauuc uuucuugagu ggcggaagca gauacacauu 241 cuccgacgga ggagaggcuu ggcuacagcc uggcaaaccg gcaagucaca aaaaaggcaa 301 uggacuccau uggggucucu auggcuaugu agugcucaug uaguucuucu ugcuguagaa 361 uguaauaaua aacaaaguug gucuuccuuu ugagaaguua ccagcuuuug cuguccaaaa 421 uuacucaauu ugcagcugac uagaauuccu uucucucuuc aguuucugca gaugaguagg 481 uaggcaauuu gugaucacuc ccuucccuuu ucaugucuuc uguguucccu uuuccaugcu 541 uguuuguguu guuaguuaug accuuaugag gaaauaaaag aauaguacaa uucuaguccc 601 ucaguuuagg auuguauucu auugaacuuu auuagaaaag uuuccagagu ccuuucuaaa 661 aaaaaaaaaa aaaaaaaaa Peptide (highlighted) UUUUUUUUUUUUU MetluLeuysTrpLeuThrThrIleislySerSTP Peptide (underlined) UUUUUagaagcuuggagagaaaggggugugagaggagagggugcucacuccucacacucccucacuuaa MetValLeulululaTrprglurglyValrglylulylaisSerSerisSerLeuThrSTP Introduction to ioganic hemistry and hemical iology 4118 *nswer 431 Most aminecontaining buffers are tertiary trialkylamines that can fm stable adducts through acylation sulfonylation Tris is a primaryl alkylamine that can react readily with DEP to fm stable carbamates + 2 Et Et Tris p 8 Introduction to ioganic hemistry and hemical iology 4121 Et