cayey november 6 2014
TRANSCRIPT
Antibacterial Agents:Synthesis of Cicadapeptins
Professor Felix M. Rivas RiveraNovember 6, 2014
Cayey P.R.
My Story
Graduated from UPR‐Cayey in 1996How did I get here?
Education
High School: Maestro Ladi, Vega Alta, Puerto Rico• Participated in Science Competitions
• Took Extra Science and Math Courses
Bachelor of Science in Chemistry: Universidad de Puerto Rico – Cayey• Participated in Undergraduate Research
• Honors College• Undergraduate Thesis
• President of Chemistry Club
Education (continued)Doctor of Philosophy in Chemistry: University of Buffalo – SUNY
• Synthesis of Organic Molecules for use as Catalysts• Ford Foundation Pre‐Doctoral Fellowship
Post‐Doctoral Studies in Medicinal Chemistry: University of Wisconsin – MilwaukeeSynthesis of Organic Molecules for use as Anti‐Seizure Agents
N
N
Real World (Education Continued!)
Instructor of Organic Chemistry – Chicago State University 2006
Assistant Professor of Chemistry – Chicago State University 2006
Assistant Professor of Chemistry Tenured – Chicago State University 2012
Associate Professor of Chemistry – Chicago State University 2013
Department of Chemistry, Physics and Engineering Studies
Research Interests
OCl
Anthocyanin(flavylium ion)
OH
HO
R
R'
Synthesis of Dyes for Dye Sensitized Solar Cells Synthesis of Antibacterial Agents
NH
HN
NH
HN
NH
HN
N
N
O
NH2O
O
O
O
O
O
O
R1
R2
HO
HO
NH2O
1: R1 = CH3, R2 = H Cicadapeptin I2: R1 = H, R2 = CH3 Cicadapeptin II
Synthesis of New Ligands for OrganometallicChemistry Catalyzed Organic Reactions
Example of Antibacterial Agents
quinolone
tetracycline
penicillin
Erythromycin
Antibacterial Agents: Synthesis of Cicadapeptins
Abstract• Cicadapeptins are short sequences of seven amino acids isolated
from the Entomopathogenic Fungus Cordyceps heteropoda. Among the unique amino acids present in Cicadapeptins are two aminoisobutyric acids and two hydroxyproline amino acids. Preliminary studies showed that Cicadapeptins act as good antibacterial agents against Bacillus cereus, B. subtilis, and Escherichia coli. In agar disk/diffusion assays using 100 mg/disk, Cicadapeptins I and II produced clear kill zones against Bacillus cereus (12‐13 mm), B. subtilis (11‐13 mm), and Escherichia coli (16 mm). To further explore their antibacterial properties their synthesis was started using solid‐supported organic synthesis. A polystyrene‐based resin with 2‐chlorotrityl chloride as linker was used. Two fragments of three amino acids each were synthesized. The synthetic approach, experimental procedure and results will be presented.
Take home messages
Synthesis of antibacterial peptide with unique amino acids
A career as a researcherand/or professor is possible for
Cicadapeptins from Fungus that infects Cicadas
Cicadapeptins
isolated from fungus on Cicadasshort peptideα‐Helical structureunique amino acidsantibacterial properties
310‐helix side view
310‐helix top view
Building!
Synthesis of Cicadapeptins
NH
HN
NH
HN
NH
HN
N
N
O
NH2O
O
O
O
O
O
O
R1
R2
HO
HO
NH2O
H2NHN
NH
H2NNH
HN
N
N
O NH2O
O
O
O
O
O
O
R1
R2
HO
HO
NH2O
OH
OH
Fragment A
Fragment B
Fragment C
Peptide Bond Formation
HN
OH
Fmoc
O
H2N
ORO
+
HN
ORO
HNFmoc
O
New Bond Made
+ H2O
HOMEWORKHow does this reaction occur?
How does your body performs this reaction a million times?
Synthesis of Fragment A
HN
O
OH
NH O
OH
HN
OHDIPEA,CH2Cl2
HN
NH
HN
O
O
Fragment A
1
4
HOBt, DIC, DMF
Fmoc
Fmoc
HOBt, DIC, DMF
Fmoc
O
resinFmoc
O
HN
O
Fmoc
O
piperidine H2N
OO
HN
OO
NH O
Fmoc
piperidine
HN
OO
H2NO
O
Synthesis of Fragment B
NH O
OH
i)
iii)
4, HOBt, DICDMF
5
FmocNH
HN
NH
O
O
O
O
HNO
Fmoc
C(Ph)3
ii) Piperidine (50%)
NH
OH
O
HNO
H2NO
O
HNO
2
C(Ph)3
Fmoc
C(Ph)3
DIPEA,CH2Cl2
i
ii Piperidine (50%)
resin
Fragment B
Experimental Procedure
Solid Phase Synthesis
• Solid Support• Solvents• Amino Acids• Coupling Reagents• Glassware• Reaction Monitoring• Purification Techniques• Instrumentation for Characterization
Future Work
H2NHN
NH
HN
NH
HN
NH
O
O
O
O
O
R1
R2
NH2O
Fragment A N
N
O
O
O
Fragment B
i) HOBt, DIC, DMF
+ NH
HN N
HOH
O
O
O
NH2O
Fragment A''(Western Hemisphere)
FmocHN
NH
HN
O
O
R1
R2
Fragment A'(Eastern Hemisphere)
Fmoc
NH
i) HOBt, DIC, DMF
ii) Piperidine (50%)
OH
OO
ii) removal from solid support andremoval of protecting groups (PG)
PG
PG
Cicadapeptins I and II
Summary and take home messages
Synthesis of antibacterial peptide with unique amino acids
A career as a researcherand/or professor is possible for
Acknowledgements
Department of ChemistryPhysics and Engineering Studies
Undergraduate Students
Zandra Floyd
George Howell
Alumni from Rivas LabValentin Torres B.S. Biology; Teacher at Chicago Public SchoolsZandra Floyd B.S. Chemistry; MS‐Chemistry IIT; Nuclear ChemistGeorge Howell B.S. Chemistry; Working for CargillSamuel Ntrakwa B.S. Chemistry; MS‐Public Health AustraliaLaurence Quinn B.S. Chemistry; Chemist, Applying to Graduate SchoolsCharity Burgos B.S. Chemistry, Graduate student at Atlanta UniversityChirag Thakar B.S. Biology; Pharm. D. Ohio State Univ., Pharmacist at Ohio, USKiel Wash H.S. Morgan Academy High School, Engineering Major IITRachel Hawkins B.S. Chemistry; Working for CargillIsabel Anaya B.S. Biology; Chicago State University, Senior Class 2015Horace James B.S. Chemistry; Chicago State University, Senior Class 2014Valencia Keys B.S. Psychology; Chicago State University, Senior Class 2015Britice Goins Pre‐Pharm.; Pharmacy School at Chicago State UniversityVeronica Smart B.S. Chemistry; Chicago State University, Senior Class 2016Patrick Adamptey B.S. Chemistry; Chicago State University, Senior Class 2016Alan Toledo B.S. Chemistry; Chicago State University, Senior Class 2015Ylse Benitez B.S. Biology; Chicago State University, Senior Class 2016
Other StudentsBonnie Gumkoski M.S.; University of Illinois Dietetics ProgramAgnes Kisai Applying to Medical SchoolSitatian Rush M.S.; Rush University, Chicago Pablo Guzman Ph.D.; Emory UniversityTameka Barlett Summer Pre‐Dentistry ProgramTabatha Williams Medical School Wisconsin MadisonLuis Rivera Medical SchoolRuth Osborne University of Illinois at Chicago PREPKatie Stanislowski Pharmacy School Chicago State University
How to get where I am now? Answer: A Lot of People Helped Me!
At Cayey the Academic SideDr. Robert RossMs. Rosita BaezDr. Mirtha TrujilloDr. Luz E. TorresDr. Wilfredo RestoDr. Mercedes RiveraDr. Genaro OrtizDr. Jairo PardoDr. Juan EstevezDr. Edgar LleraDr. Nestor Carballeira (UPR‐RP)Dr. Alba Reyes (Graduate Student)Dr. Mayra Pagan (Graduate Student)Dr. Carmen UmpierreAll other Professors in the Sciences
UPR‐Cayey Honors Program
Dr. Angel Lopez (student)
How to get where I am now? Answer: A Lot of People Helped Me!
At Cayey the Non‐Academic SideMBRS Office StaffDr. Glamarie Burgos (student)Students from Chemistry ClubStudents and faculty from BBBUPR‐Cayey Honors Program Staff
At SUNY Buffalo:Dr. Luis A ColonDr. Steven T. DiverDr. John RichardFord Foundation Pre‐DoctoralDr. Glamarie Burgos (student)Students at Steven T. Diver Lab
At University of Wisconsin:Dr. James CookDr. Luis A. ColonDr. Glamarie BurgosStudents at James Cook Lab
At Chicago State University:Dr. LeRoy Jones Dr. Mel SabellaDr. Luis A. Colon Dr. Mike MimnaughDr. David Kanis Dr. Mark E. DubanDr. Glamarie Burgos Mr. Ismael ReynaMr. Fernando Diaz Ms. Leticia CarilloDr. Pablo Guzman Ford Foundation Senior Fellows
I still need HELP!
It is OK to ask and accept HELP, you will need it!
Take Home MessagePart II
Chicago