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1
Outline



          Market & Technology Trends

          LifeTein Technology Portfolio

          LifeTein Services




                                          2
Synthetic Therapeutic Peptides




More than 60 synthetic therapeutic peptides under 50 amino acids in
size have reached the pharmaceutical market as APIs or generics.      3
Chemical Optimization




                             Drug Discovery Today Volume 15, Numbers 1/2 January 2010



        Strategies for Lead Peptide Optimization                                        4
Technology Trends



                                               Microwave Synthesis




                                               Using Nitroalkanes as Acyl Anion
                                               Equivalents
www.nature.com/doifinder/10.1038/nature09125




                                               Green Chemistry for Synthesis
                                                                                  5
LifeTein Technology Portfolio


                                PeptideSynTM Platform

                                  Provides high-yield
                                peptide synthesis

                                  Combines SPPS and
                                LPPS for the highest
                                synthesis success rate
                                possible

                                  Ensures shorter
                                turnaround



                                                    6
LifeTein Technology Portfolio




                                PeptideSynTM Ligation

                                  Synthesizes long
                                peptides (up to 120
                                amino acids)

                                  Ensures high yield and
                                short turnaround




                                                      7
LifeTein Technology Portfolio




                                A: H-MEDSTYYKASKGC-NH2
                                B: H-MEDST(PTyr)YKASKGC-NH2
                                C: H-PKYLQNTLKLATGMRNVPEKQTT-OH
                                D: H-MEDSTYYKASKGC-NH2
                                E: H-MEDST(PTyr)YKASKGC-NH2
                                F: H-PKYLQNTLKLATGMRNVPEKQTT-OH




                                                          8
LifeTein Services



        Custom Peptide Synthesis Service

        Custom Peptide Library Synthesis Service

        Custom Polyclonal Antibody Service

        Custom Monoclonal Antibody Service




                                                   9
LifeTein Services

            Advantages of PeptideSynTM Technology

  Increases yields and reduces costs

  Shortens production cycle

  Combines the advantages of both solid and solution phase methods

  Can scale up projects rapidly to over 100 kg

  Avoids solubility problems for long segments in solution phase




                                                                     10
Peptide Synthesis Service

Peptide Length      5-120 amino acids

 Peptide Scale      From mg to kg

 Peptide Purity     Crude, desalted, >75%, >85%, >90%, >95%, 98%, and >99%

   Peptide
                    2-5 phosphorylation sites, methylation, acetylation, amidation, MAPs(2, 4 or 8 chains), more…
 Modifications

 Peptide Labels     FITC, Biotin, 5-FAM, Rhodamine, Dansyl, TAMRA, more…

Carrier Proteins    KLH, BSA, OVA

Cyclic Peptides     Amide cyclic peptide (head to tail, side chain), 1, 2, or 3 disulfide bond bridges

    Analysis        HPLC, MS, Amino Acid Analysis (AAA), solubility testing, microbial analysis, more…

Peptide Libraries   Peptide sequence length of 5-20 amino acids, 48, 96 peptides

     Others         Free aliquots, spacers and linkers (Ahx, mini-PEG), more…




                                                                                                             11
Free Aliquot Service




                       12
Case Studies

                       Cell Penetrating Peptides

         Name                    Origin                   Sequence
   Tat family

       Tat (48-60)             HIV-1 protein          GRKKRRQRRRPPQQ

       Oligoarginine           Tat derivative                Rn

   Penetralia family

          p-Antp         Antermapedia homeodomain     RQIKIWFQNRRMKWKK
            plsl            Igl-1 homeodomain         RVIRVWFQNKRCKDKK

   Chimeric CPPs

                                                    GWTLNSAGYLLGKINLKALAA
        Transportan         Galanin-mastoparan
                                                           LAKKIL




                                                                            13
Case Studies
                      Cell Penetrating Peptides




Attached to a CPP, therapeutic cargo is delivered to an intracellular target,
thus overcoming the entry restrictions set by the plasma membrane.              14
Case Studies

           N-Terminal Acetylation and C-Terminal Amidation
                                 Both modifications are free of charge




Chemically synthesized peptides have free amino and carboxyl termini.

N-terminal acetylation and C-terminal amidation reduce the overall charge of the peptide. This can   15
increase the stability of the peptide and its resemblance to the native protein.
Peptide Antigen Design




Continuous versus Discontinuous Epitopes?




                                            16
Peptide Antigen Design

 Sequence Length            8-20 amino acids

                        •   >75% for antibody generation,
   Peptide Purity
                        •   >90% for phosphorylated peptide antibody (recommended)

                        •   Keep the hydrophobic amino acid content below 50%
 Peptide Solubility
                        •   At least one charged residue for every five amino acids

                        • Cys and Met can undergo rapid oxidation
Difficult Amino Acids   • Avoid multiple Ser or Pro
                        • Avoid multiple or adjacent β-sheet forming amino acids: Glu, Iso, Leu, Phe, Thr, Tyr, Val

  Carrier Proteins          KLH, BSA, OVA




                                            Multiple Antigenic Peptides (MAPs)
                                                                                                              17
Custom Antibody Service

                                                        • Polyclonal Antibodies
         Peptide Antigen Antibody Services
                                                        • Monoclonal Antibodies


                                                        • Polyclonal Antibodies
      Phosphorylated-Peptide Antibody Services
                                                        • Monoclonal Antibodies


                                                        • Polyclonal Antibodies
        Methylated-Peptide Antibody Services
                                                        • Monoclonal Antibodies




                    AdjuBoosterTM Adjuvant Technology

                                                                           18
More information, please visit www.lifetein.com   19
Contact Information


              LifeTein LLC
              150 Maple Ave
              South Plainfield, NJ 07080
              USA


              info@lifetein.com

              1-732-444-3282
              1-888-791-1618 (Toll Free)

              1-888-791-1618 (Fax)




     Let us be a partner to your growth!

                                           20

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Custom peptide synthesis services

  • 1. 1
  • 2. Outline Market & Technology Trends LifeTein Technology Portfolio LifeTein Services 2
  • 3. Synthetic Therapeutic Peptides More than 60 synthetic therapeutic peptides under 50 amino acids in size have reached the pharmaceutical market as APIs or generics. 3
  • 4. Chemical Optimization Drug Discovery Today Volume 15, Numbers 1/2 January 2010 Strategies for Lead Peptide Optimization 4
  • 5. Technology Trends Microwave Synthesis Using Nitroalkanes as Acyl Anion Equivalents www.nature.com/doifinder/10.1038/nature09125 Green Chemistry for Synthesis 5
  • 6. LifeTein Technology Portfolio PeptideSynTM Platform Provides high-yield peptide synthesis Combines SPPS and LPPS for the highest synthesis success rate possible Ensures shorter turnaround 6
  • 7. LifeTein Technology Portfolio PeptideSynTM Ligation Synthesizes long peptides (up to 120 amino acids) Ensures high yield and short turnaround 7
  • 8. LifeTein Technology Portfolio A: H-MEDSTYYKASKGC-NH2 B: H-MEDST(PTyr)YKASKGC-NH2 C: H-PKYLQNTLKLATGMRNVPEKQTT-OH D: H-MEDSTYYKASKGC-NH2 E: H-MEDST(PTyr)YKASKGC-NH2 F: H-PKYLQNTLKLATGMRNVPEKQTT-OH 8
  • 9. LifeTein Services Custom Peptide Synthesis Service Custom Peptide Library Synthesis Service Custom Polyclonal Antibody Service Custom Monoclonal Antibody Service 9
  • 10. LifeTein Services Advantages of PeptideSynTM Technology Increases yields and reduces costs Shortens production cycle Combines the advantages of both solid and solution phase methods Can scale up projects rapidly to over 100 kg Avoids solubility problems for long segments in solution phase 10
  • 11. Peptide Synthesis Service Peptide Length 5-120 amino acids Peptide Scale From mg to kg Peptide Purity Crude, desalted, >75%, >85%, >90%, >95%, 98%, and >99% Peptide 2-5 phosphorylation sites, methylation, acetylation, amidation, MAPs(2, 4 or 8 chains), more… Modifications Peptide Labels FITC, Biotin, 5-FAM, Rhodamine, Dansyl, TAMRA, more… Carrier Proteins KLH, BSA, OVA Cyclic Peptides Amide cyclic peptide (head to tail, side chain), 1, 2, or 3 disulfide bond bridges Analysis HPLC, MS, Amino Acid Analysis (AAA), solubility testing, microbial analysis, more… Peptide Libraries Peptide sequence length of 5-20 amino acids, 48, 96 peptides Others Free aliquots, spacers and linkers (Ahx, mini-PEG), more… 11
  • 13. Case Studies Cell Penetrating Peptides Name Origin Sequence Tat family Tat (48-60) HIV-1 protein GRKKRRQRRRPPQQ Oligoarginine Tat derivative Rn Penetralia family p-Antp Antermapedia homeodomain RQIKIWFQNRRMKWKK plsl Igl-1 homeodomain RVIRVWFQNKRCKDKK Chimeric CPPs GWTLNSAGYLLGKINLKALAA Transportan Galanin-mastoparan LAKKIL 13
  • 14. Case Studies Cell Penetrating Peptides Attached to a CPP, therapeutic cargo is delivered to an intracellular target, thus overcoming the entry restrictions set by the plasma membrane. 14
  • 15. Case Studies N-Terminal Acetylation and C-Terminal Amidation Both modifications are free of charge Chemically synthesized peptides have free amino and carboxyl termini. N-terminal acetylation and C-terminal amidation reduce the overall charge of the peptide. This can 15 increase the stability of the peptide and its resemblance to the native protein.
  • 16. Peptide Antigen Design Continuous versus Discontinuous Epitopes? 16
  • 17. Peptide Antigen Design Sequence Length 8-20 amino acids • >75% for antibody generation, Peptide Purity • >90% for phosphorylated peptide antibody (recommended) • Keep the hydrophobic amino acid content below 50% Peptide Solubility • At least one charged residue for every five amino acids • Cys and Met can undergo rapid oxidation Difficult Amino Acids • Avoid multiple Ser or Pro • Avoid multiple or adjacent β-sheet forming amino acids: Glu, Iso, Leu, Phe, Thr, Tyr, Val Carrier Proteins KLH, BSA, OVA Multiple Antigenic Peptides (MAPs) 17
  • 18. Custom Antibody Service • Polyclonal Antibodies Peptide Antigen Antibody Services • Monoclonal Antibodies • Polyclonal Antibodies Phosphorylated-Peptide Antibody Services • Monoclonal Antibodies • Polyclonal Antibodies Methylated-Peptide Antibody Services • Monoclonal Antibodies AdjuBoosterTM Adjuvant Technology 18
  • 19. More information, please visit www.lifetein.com 19
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