?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10618%2F&rft.title=Designing+Methodology+for+the+Incorporation+of+Beta-Amino+Acids+into+Protein+Tertiary+Structures&rft.creator=Lengyel%2C+George&rft.description=The+goal+of+this+project+is+to+explore+methodologies+applicable+to+introducing+%CE%B2-amino+acid+residues+into+%0D%0Anatural+protein+sequences+with+well-defined+tertiary+structures+while+maintaining+the+folded+structure+of+%0D%0Athese+natural+sequences.++Hybrid+%CE%B1%2F%CE%B2-peptides+synthesized+with+%CE%B2-amino+acids+have+additional+rotational+%0D%0Afreedom+of+their+backbone+and+also+have+increased+resistance+to+proteolysis+relative+to+natural+%CE%B1-peptides.++%0D%0A16+unnatural+%CE%B2-amino+acids+with+varied+stereochemistry+and+torsional+restraints+were+synthesized+using+a+%0D%0Avariety+of+published+literature+methods.++A+peptide+model+system+known+to+fold+into+a+%CE%B2-hairpin+secondary+%0D%0Astructure+in+aqueous+solution+was+chosen+for+substitution+with+the+unnatural+residues+at+two+positions.++%0D%0AUsing+Fmoc+solid-phase+peptide+synthesis%2C+16+hybrid+%CE%B1%2F%CE%B2-peptides+as+well+as+16+unfolded+control+peptides+%0D%0Awere+synthesized+and+studied+by+2D+NMR.++Using+the+NMR+data+obtained+from+this+study%2C+the+mutant+%0D%0Apeptides+were+analyzed+for+indications+of+folded+population.++Three+peptides+showed+a+high+degree+of+%0D%0Afolded+population%3A+those+including+a+%CE%B23%0D%0A-amino+acid+and+two+including+the+enantiomers+of+a+trans-%0D%0Adisubstituted-%CE%B22%2C3%0D%0A-amino+acid.++NOE-derived+distance+restraints+were+established+and+high-resolution+3D+%0D%0Astructures+of+these+peptides+were+calculated.++Using+these+structures%2C+it+was+found+that+the+peptide+%0D%0Asubstituted+with+(2R%2C+3S)-3-amino-2%2C4-dimethylpentanoic+acid+most+closely+emulated+the+hairpin+structure+%0D%0Aof+the+model+system.++Currently%2C+work+is+ongoing+to+determine+the+effect+of+side-chain+functionalization+%0D%0Aand+substitution+pattern+on+the+folding+of+larger+protein+systems.&rft.date=2012-01-18&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10618%2F1%2FGAL_2011_vers2.pdf&rft.identifier=++Lengyel%2C+George++(2012)+Designing+Methodology+for+the+Incorporation+of+Beta-Amino+Acids+into+Protein+Tertiary+Structures.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++