Zwitterionic dendrimer is an effective carrier, which can restore the natural conformation of peptide segments for high bioaffinity by a hydrogen bond-induced conformational constraint approach. However, it is still unknown whether the approach is applicable for the dendrimers with different geometric sizes. Therefore, the characteristics of conjugates made from zwitterionic poly(amidoamine) (PAM) and the arginine-glycine-aspartic acid (RGD) peptide were examined to elucidate the effects of the geometric sizes of the PAM dendrimer on the conformational structure and stability of the peptide. The results show that the RGD fragments had almost the same structure and stability when conjugated with PAM(G3, G4, or G5) dendrimers. However, when conjugated with PAM(G1 or G2) dendrimers, the structural stability of these fragments was found to be much worse. Also, the structure and stability of RGD segments conjugated with PAM(G3, G4, or G5) were not affected when additional EK segments were inserted. Moreover, we observed that RGD fragments conjugated with PAM(G3, G4, or G5) dendrimers were structurally stable and similar when the concentration of NaCl was 0.15 and 0.5M. Furthermore, we show that PAM(G3, G4, or G5)-RGD conjugates bind strongly to integrin αvβ3.

1.
Q.
Cong
,
I.
Anishchenko
,
S.
Ovchinnikov
, and
D.
Baker
,
Science
365
,
185
(
2019
).
2.
R.
Freilich
,
M.
Betegon
,
E.
Tse
,
S. A.
Mok
,
O.
Julien
,
D. A.
Agard
,
D. R.
Southworth
,
K.
Takeuchi
, and
J. E.
Gestwicki
,
Nat. Commun.
9
,
4563
(
2018
).
3.
A.
Sorolla
,
E.
Wang
,
E.
Golden
,
C.
Duffy
,
S. T.
Henriques
,
A. D.
Redfern
, and
P.
Blancafort
,
Oncogene
39
,
1167
(
2020
).
4.
J.
Menche
,
A.
Sharma
,
M.
Kitsak
,
S. D.
Ghiassian
,
M.
Vidal
,
J.
Loscalzo
, and
A. L.
Barabasi
,
Science
347
,
1257601
(
2015
).
5.
D. E.
Scott
,
A. R.
Bayly
,
C.
Abell
, and
J.
Skidmore
,
Nat. Rev. Drug Discovery
15
,
533
(
2016
).
7.
M. D.
Pierschbacher
and
E.
Ruoslahti
,
Nature
309
,
30
(
1984
).
8.
V.
Neduva
and
R. B.
Russell
,
Curr. Opin. Biotechnol.
17
,
465
(
2006
).
9.
P.
Zhang
,
Y.
Cui
,
C. F.
Anderson
,
C.
Zhang
,
Y.
Li
,
R.
Wang
, and
H.
Cui
,
Chem. Soc. Rev.
47
,
3490
(
2018
).
10.
K.
Johnsson
,
R. K.
Allemann
,
H.
Widmer
, and
S. A.
Benner
,
Nature
365
,
530
(
1993
).
11.
C. F.
Barbas
,
L. R.
Languino
, and
J. W.
Smith
,
Proc. Natl. Acad. Sci. U.S.A.
90
,
10003
(
1993
).
12.
A.
Patel
,
G. V.
Toia
,
K.
Colletta
,
B. D.
Bradaric
,
P. M.
Carvey
, and
B.
Hendey
,
Exp. Neurol.
231
,
160
(
2011
).
13.
Y.
Jie
,
L.
Zaiquan
,
Y.
Tingyuan
,
W.
Jiancheng
,
Z.
Xuan
, and
Z.
Qiang
,
J. Drug Targeting
19
,
25
(
2011
).
14.
K.
Hitesh
,
P.
Deep
,
K.
Raju
,
R. T.
Srinivasa
,
T. R. F.
S
,
A. D. J.
Ravi
,
S.
Ramakrishna
, and
B.
Vipul
,
Mol. Pharm.
13
,
1491
(
2016
).
15.
R.
Chakravarty
,
S.
Chakraborty
, and
A.
Dash
,
Mini-Rev. Med. Chem.
15
,
1073
(
2015
).
16.
N. P.
McCabe
,
S.
De
,
A.
Vasanji
,
J.
Brainard
, and
T. V.
Byzova
,
Oncogene
26
,
6238
(
2007
).
17.
H.
Hamidi
and
J.
Ivaska
,
Nat. Rev. Cancer
18
,
533
(
2018
).
18.
M.
Nieberler
et al,
Cancers (Basel)
9
,
116
(
2017
).
19.
C.
Liu
and
N.
Zhang
,
Prog. Mol. Biol. Transl. Sci.
104
,
509
(
2011
).
20.
S.
Zeng
,
X.
Quan
,
H.
Zhu
,
D.
Sun
,
Z.
Miao
,
L.
Zhang
, and
J.
Zhou
,
Langmuir
37
,
1225
(
2021
).
21.
Y.
Cui
,
B.
Liang
,
L.
Wang
,
L.
Zhu
,
J.
Kang
,
H.
Sun
, and
S.
Chen
,
Mater. Sci. Eng. C
93
,
332
(
2018
).
22.
23.
D. E.
Koshland
,
Proc. Natl. Acad. Sci. U.S.A.
44
,
98
(
1958
).
24.
D. E.
Koshland
,
Angew. Chem.
33
,
2375
(
1994
).
25.
D. M.
Gakamsky
,
I. F.
Luescher
, and
I.
Pecht
,
Proc. Natl. Acad. Sci. U.S.A.
101
,
9063
(
2004
).
26.
G. G.
Hammes
,
Y. C.
Chang
, and
T. G.
Oas
,
Proc. Natl. Acad. Sci. U.S.A.
106
,
13737
(
2009
).
27.
D. D.
Boehr
,
R.
Nussinov
, and
P. E.
Wright
,
Nat. Chem. Biol.
5
,
789
(
2009
).
28.
S.
Shen
,
Y.
Wu
,
Y.
Liu
, and
D.
Wu
,
Int. J. Nanomed.
12
,
4085
(
2017
).
29.
Y.
Shen
et al,
J. Am. Chem. Soc.
132
,
4259
(
2010
).
30.
D.
Yu
et al,
J. Controlled Release
110
,
90
(
2005
).
31.
B. S.
Zolnik
,
A.
González-Fernández
,
N.
Sadrieh
, and
M. A.
Dobrovolskaia
,
Endocrinology
151
,
458
(
2010
).
32.
M.
Longmire
,
P. L.
Choyke
, and
H.
Kobayashi
,
Nanomedicine
3
,
703
(
2008
).
33.
S.
Chen
,
Z.
Cao
, and
S.
Jiang
,
Biomaterials
30
,
5892
(
2009
).
34.
V.
Maingi
,
V.
Jain
,
P. V.
Bharatam
, and
P. K.
Maiti
,
J. Comput. Chem.
33
,
1997
(
2012
).
35.
D. A.
Case
et al,
AmberTools 16
(
University of California
,
San Francisco
,
2016
).
36.
M. Z.
Tien
,
D. K.
Sydykova
,
A. G.
Meyer
, and
C. O.
Wilke
,
PeerJ
1
,
e80
(
2013
).
37.
M. J.
Frisch
et al,
Gaussian 16 Rev. C.01
(Gaussian, Inc.,
Wallingford, CT
,
2016
).
38.
J. A.
Maier
,
C.
Martinez
,
K.
Kasavajhala
,
L.
Wickstrom
,
K. E.
Hauser
, and
C.
Simmerling
,
J. Chem. Theory Comput.
11
,
3696
(
2015
).
39.
A. W.
Sousa da Silva
and
W. F.
Vranken
,
BMC Res. Notes
5
,
367
(
2012
).
40.
G.
Bussi
,
D.
Donadio
, and
M.
Parrinello
,
J. Chem. Phys.
126
,
014101
(
2007
).
41.
M.
Parrinello
and
A.
Rahman
,
J. Appl. Phys.
52
,
7182
(
1981
).
42.
B.
Hess
,
H.
Bekker
,
H. J.
Berendsen
, and
J. G.
Fraaije
,
J. Comput. Chem.
18
,
1463
(
1997
).
43.
U.
Essmann
,
L.
Perera
,
M. L.
Berkowitz
,
T.
Darden
,
H.
Lee
, and
L. G.
Pedersen
,
J. Chem. Phys.
103
,
8577
(
1995
).
44.
M. J.
Abraham
,
T.
Murtola
,
R.
Schulz
,
S.
Páll
,
J. C.
Smith
,
B.
Hess
, and
E.
Lindahl
,
SoftwareX
1–2
,
19
(
2015
).
45.
F.
Chen
,
H.
Liu
,
H.
Sun
,
P.
Pan
,
Y.
Li
,
D.
Li
, and
T.
Hou
,
Phys. Chem. Chem. Phys.
18
,
22129
(
2016
).
46.
H.
Ding
,
Y.
Yin
,
S.
Ni
,
Y.
Sheng
, and
Y.
Ma
,
Chin. Phys. Lett.
38
,
018701
(
2021
).
47.
S.
Genheden
and
U.
Ryde
,
Proteins
80
,
1326
(
2012
).
48.
E. W.
Rusche
and
W. B.
Good
,
J. Chem. Phys.
45
,
4667
(
1966
).
49.
See supplementary material online for the concrete methods of coordinate transformation of conjugates.

Supplementary Material

You do not currently have access to this content.