337
3. In the specific reactions we used DMSO-d 6 to characterize the
purity of the compounds due to solubility. In other cases,
other deuterated solvents can be used as well.
4. HATU should be used in a ratio of 1:1 with the aminoacid
since excess quantity can form unwanted side products [9].
5. TFA cleavage cocktail is used to cleave the Boc-groups of
gemcitabine. If another drug is used that is not Boc-protected,
this step is not required.
6. If more peaks appear during HPLC purification, collect and
lyophilize all and then characterize all starting from the major
one, until you identify the expected product.
7. Usually the addition of DMSO or aniline-based catalysts are
mandatory for the reaction to proceed.
Acknowledgments
This research was co-financed by Greece and the European Union
(European Social Fund- ESF) through the Operational Program
“Human Resources Development, Education and Lifelong
Learning 2014–2020” in the context of the project “Strengthening
Human Resources Research Potential via Doctorate Research -
second Cycle” (MIS 5000432). The research work was supported
by the Hellenic Foundation for Research and Innovation (H.F.R.I.)
under the “First Call for H.F.R.I. Research Projects to support
Faculty members and Researchers and the procurement of highcost research equipment grant” (Project Number: 991, acronym
PROTECT).
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL,
Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence
and mortality worldwide for 36 cancers in 185
countries. CA Cancer J Clin 68:394–424
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E,
Forman D (2011) Global cancer statistics. CA
Cancer J Clin 61:69–90
3. Szakacs G, Paterson JK, Ludwig JA, BoothGenthe C, Gottesman MM (2006) Targeting
multidrug resistance in cancer. Nat Rev Drug
Discov 5:219–234
4. Vrettos EI, Mezo G, Tzakos AG (2018) On the
design principles of peptide-drug conjugates
for targeted drug delivery to the malignant
tumor site. Beilstein J Org Chem 14:930–954
5. Wang YF, Liu L, Xue X, Liang XJ (2017)
Nanoparticle-based drug delivery systems:
what can they really do in vivo? F1000 Res
6:681
6. Kalimuthu K, Lubin B-C, Bazylevich A,
Gellerman G, Shpilberg O, Luboshits G,
Firer MA (2018) Gold nanoparticles stabilize
peptide- drug-conjugates for sustained targeted
drug delivery to cancer cells. J Nanobiotechnol
16:34–34
7. Fan Q, Ji Y, Wang J, Wu L, Li W, Chen R,
Chen Z (2018) Self-assembly behaviours of
peptide-drug conjugates: influence of multiple
factors on aggregate morphology and potential self-assembly mechanism. R Soc Open Sci
5:172040–172040
8. Chang R, Zou Q, Xing R, Yan X (2019)
Peptide-based supramolecular nanodrugs as
a new generation of therapeutic toolboxes
against cancer. Adv Ther 2:1900048
Construction of Peptide-Drug Conjugates for Selective Targeting of Malignant Tumor Cells
3. In the specific reactions we used DMSO-d 6 to characterize the
purity of the compounds due to solubility. In other cases,
other deuterated solvents can be used as well.
4. HATU should be used in a ratio of 1:1 with the aminoacid
since excess quantity can form unwanted side products [9].
5. TFA cleavage cocktail is used to cleave the Boc-groups of
gemcitabine. If another drug is used that is not Boc-protected,
this step is not required.
6. If more peaks appear during HPLC purification, collect and
lyophilize all and then characterize all starting from the major
one, until you identify the expected product.
7. Usually the addition of DMSO or aniline-based catalysts are
mandatory for the reaction to proceed.
Acknowledgments
This research was co-financed by Greece and the European Union
(European Social Fund- ESF) through the Operational Program
“Human Resources Development, Education and Lifelong
Learning 2014–2020” in the context of the project “Strengthening
Human Resources Research Potential via Doctorate Research -
second Cycle” (MIS 5000432). The research work was supported
by the Hellenic Foundation for Research and Innovation (H.F.R.I.)
under the “First Call for H.F.R.I. Research Projects to support
Faculty members and Researchers and the procurement of highcost research equipment grant” (Project Number: 991, acronym
PROTECT).
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL,
Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence
and mortality worldwide for 36 cancers in 185
countries. CA Cancer J Clin 68:394–424
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E,
Forman D (2011) Global cancer statistics. CA
Cancer J Clin 61:69–90
3. Szakacs G, Paterson JK, Ludwig JA, BoothGenthe C, Gottesman MM (2006) Targeting
multidrug resistance in cancer. Nat Rev Drug
Discov 5:219–234
4. Vrettos EI, Mezo G, Tzakos AG (2018) On the
design principles of peptide-drug conjugates
for targeted drug delivery to the malignant
tumor site. Beilstein J Org Chem 14:930–954
5. Wang YF, Liu L, Xue X, Liang XJ (2017)
Nanoparticle-based drug delivery systems:
what can they really do in vivo? F1000 Res
6:681
6. Kalimuthu K, Lubin B-C, Bazylevich A,
Gellerman G, Shpilberg O, Luboshits G,
Firer MA (2018) Gold nanoparticles stabilize
peptide- drug-conjugates for sustained targeted
drug delivery to cancer cells. J Nanobiotechnol
16:34–34
7. Fan Q, Ji Y, Wang J, Wu L, Li W, Chen R,
Chen Z (2018) Self-assembly behaviours of
peptide-drug conjugates: influence of multiple
factors on aggregate morphology and potential self-assembly mechanism. R Soc Open Sci
5:172040–172040
8. Chang R, Zou Q, Xing R, Yan X (2019)
Peptide-based supramolecular nanodrugs as
a new generation of therapeutic toolboxes
against cancer. Adv Ther 2:1900048
Construction of Peptide-Drug Conjugates for Selective Targeting of Malignant Tumor Cells