Peptide dendrimers as antifungal agents and carriers for potential antifungal agent—N3-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic acid—synthesis and antimicrobial activity

Article abstract of DOI:10.1002/psc.3226

A series of peptide dendrimers and their conjugates with antimicrobial agent FMDP (N³-(4-methoxyfumaroyl)-(S)-2,3-diamino-propanoic acid) were synthesized. The obtained compounds were tested for the antibacterial and antifungal activity. All no

Full text of DOI:10.1002/psc.3226

R A P I D C O M M U N I C A T I O N
Peptide dendrimers as antifungal agents and carriers for
potential antifungal agent—N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐
diaminopropanoic acid—synthesis and antimicrobial activity
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Magdalena Stolarska Katarzyna Gucwa Zofia Urbańczyk‐Lipkowska
Ryszard Andruszkiewicz
A series of peptide dendrimers and their conjugates with antimicrobial agent FMDP
(N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐diamino‐propanoic acid) were synthesized. The obtained
compounds were tested for the antibacterial and antifungal activity. All novel dendrimers
displayed much better activity against the tested strains than FMDP itself. The most
promising molecules were tested against a broad selection of fungal strains. The analysis
of their antifungal properties indicates that the examined molecules are efficient growth
inhibitors of fluconazole‐resistant hospital‐acquired strains.
Wiley Online Library Graphical TOC

Received: 14 June 2019
DOI: 10.1002/psc.3226
Revised: 27 September 2019
Accepted: 1 October 2019
R A P I D C O M M U N I C A T I O N
Peptide dendrimers as antifungal agents and carriers for
potential antifungal agent—N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐
diaminopropanoic acid—synthesis and antimicrobial activity
Magdalena Stolarska3
Katarzyna Gucwa1
Zofia Urbańczyk‐Lipkowska2
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Ryszard Andruszkiewicz1
1 Faculty of Chemistry, Gdańsk University of
Technology, Gdańsk, Poland
2 Institute of Organic Chemistry, Polish
Academy of Science, Warsaw, Poland
A series of peptide dendrimers and their conjugates with antimicrobial agent FMDP
(N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐diamino‐propanoic acid) were synthesized. The
obtained compounds were tested for the antibacterial and antifungal activity. All
novel dendrimers displayed much better activity against the tested strains than
FMDP itself. Moreover, their conjugates with FMDP also exhibited antimicrobial
activity. The most promising molecules were tested against a broad selection of fun-
gal strains. The analysis of their antifungal properties indicates that the examined
molecules are efficient growth inhibitors of fluconazole‐resistant hospital‐acquired
strains. Moreover, an application of amphiphilic branched peptides such as FMDP
carriers suggests that transport mechanism involves more likely the cell membrane
perturbation than the mediation of the specific transport proteins. The activity of
obtained compounds strongly depends on the specific structure of the molecule.
3 National Medicines Institute, Warszaw,
Poland
Correspondence
Magdalena Stolarska, National Medicines
Institute, Chełmska 30/34, 00‐725 Warszaw,
Poland.
Email: m.stolarska@nil.gov.pl
KEYWORDS
antimicrobial activity, drug delivery, FMDP, peptide dendrimers
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1
INTRODUCTION
membrane, whose structure varies depending on organism (ergosterol
for fungi and cholesterol for mammals).4,5 Due to these differences, it
An increasing number of fungal infections is a serious problem in
today's world.1 Candidiasis is considered to be one of the most diffi-
cult chronic diseases to be treated effectively. Systemic fungal infec-
tions are particularly dangerous for affected patients. Nowadays, the
commonly occurring phenomenon of antibiotics abuse, the body ster-
ilization, and immunodeficiency diseases are the main factors causing
the increased number of severe and difficult to cure cases of candidi-
asis.2 Moreover, there is a limited range of available antifungal drugs
on the market; however, many of them, such as amphotericin B, are
highly toxic and display a number of side effects. Therefore, there is
an explicit need for new antifungals that would lead to effective
therapy.3,4
is possible to develop a selective antifungal drug.6 As another poten-
tial target for the design of antifungal agents, we proposed glucos-
amine‐6‐phosphate (GlcN‐6‐P) synthase, which catalyzes the first
step in the biosynthesis of uridine diphosphate N‐acetylglucosamine
(UDP‐GlcNAc), a precursor of a number of aminosugars containing
macromolecules including chitin and mannoproteins in fungi.7
The
N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐diamino‐propanoic
acid
(FMDP), the most selective and effective inhibitor of GlcN‐6‐P syn-
thase,8 was proposed as an antifungal agent. Although this compound
has shown the high activity against the pure enzyme, it displayed,
however, only a very poor antimicrobial activity. This effect is likely
caused by the high polarity of the inhibitor molecule which prevents
its effective penetration through the cell wall.8 The modifications of
the inhibitor molecule by increasing its lipophilicity,9,10 synthesis of
The differences in the structures between the fungal and mamma-
lian cells must be taken into account before selecting a specific molec-
ular target in drug design. An example of such target is a cellular
latent ester derivatives,11 12
,
and FMDP incorporation into short
1 of 7
J Pep Sci. 2019;e3226.
wileyonlinelibrary.com/journal/psc
© 2019 European Peptide Society and John Wiley & Sons, Ltd.
https://doi.org/10.1002/psc.3226

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STOLARSKA ET AL.
peptides were also tested.13 However, none of these approaches has
so far provided the expected results.
the possibility of using them as drug carriers in pharmacology and in
gene therapy 14-21or as an antimicrobial agents by themselves.22
In this communication, we report the synthesis of novel Lys‐based
peptide dendrimers and their conjugates with FMDP and evaluation of
their antimicrobial and antifungal activity.
Therefore, the development of suitable FMDP carrier, a molecule
capable of transporting active compound to its site of action and
releasing it there, might solve the problem. For this purpose, we pro-
posed to design a group of polyfunctional, amphiphilic peptide
dendrimers that are carrying multiple positive charges and two or four
FMDP residues located at terminal positions. Dendrimers, in general,
are a vast family of nanosized cascade molecules with branched struc-
ture and multiple chemical functionalities on the surface. Due to their
properties, dendrimers such as polyamidoamine (PAMAM's) or poly
(amidoamine‐organosilicone) (PAMAMOS) and other constructed from
amino acids (Lys, Orn, and Arg) are widely used in many applications,
including drug delivery. Interestingly, dendrimers themselves may also
be used as antimicrobial agents. There are many literature reports on
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2
SYNTHESIS OF PEPTIDE DENDRIMERS
The synthesis of peptide dendrimers (Schemes 1 and 2) was carried
out by the divergent method by the active esters, giving oily products
in acceptable yields. Obtained cascade molecules were used as a
transport system for the selective GlcN‐6‐P synthase inhibitor, ie,
FMDP molecule, which was obtained by the known procedure,8 or
alone as active agents themselves. Deprotection of the Boc groups
SCHEME 1 Synthesis of dendrimers 8 and
13 and their conjugates with FMDP. (A)
dodecylamine (DDA), THF, rt, 24 h, yield: 90%
(2), 89% (10); (B) HCl/dioxane, rt, 4 h, yield:
92% (4), 90% (11); (C) MeOH/water, rt, 24 h;
(D) HCl/dioxane, rt, 4 h, yield: 90% (6), 90%
(12); (E) MeOH/water, rt, 24 h; (F) H2, Pd/C,
rt, 4 h, yield: 72% (8), 60% (13); (G) MeOH/
water, rt, 24 h; (H) HCl/dioxane, rt, 4 h, yield:
69% (8a), 77% (13a)

STOLARSKA ET AL.
3 of 7
SCHEME 2 Synthesis of peptide dendrimers 14‐23 and their conjugates with FMDP. (A) MeOH/water, rt, 24 h, yield: 62%; (B) HCl/dioxane, rt, 4
h; (C) Cbz‐Lys (Boc)‐OSu, MeOH, rt, 24 h yield: 63%; (D) HCl/dioxane, rt, 4 h yield: 86%; (E) Ser, DDA or But‐OH, MeOH/water, rt, 24 h, yield:
67% (16), 69% (20), 89% (22); (F) HCl/dioxane, rt, 4 h; (G) methyl acrylate (MA), MeOH/water, rt, 24 h, yield: 53%; (H) EDA, MeOH/water, rt, 24 h,
yield: 65%; (I) Cbz‐Lys (Boc)‐OSu, MeOH, rt, 24 h yield: 62%; (J) HCl/dioxane, rt, 4 h yield: 86%; (K) Boc‐FMDP‐OSu, MeOH/water, rt, 24 h, (L)
HCl/dioxane, rt, 4 h yield: 85%; (M) HCl/dioxane, rt, 4 h; (N) Cbz‐Lys (Boc)‐OSu, MeOH, rt, 24 h yield: 69% (21), 68% (23); (O) HCl/dioxane, rt, 4 h
yield: 88% (21a), 93% (23a); (P) Boc‐FMDP‐OSu (7), MeOH/water, rt, 24 h; (Q) HCl/dioxane, rt, 4 h yield: 86% (21b), 81% (23b)
was carried out with 4M HCl in dioxane, providing products as amor-
phous hydrochloride salts in a good yield, while deprotection of Cbz
group was carried out by catalytic hydrogenation in the presence of
a catalyst (5% Pd/C) also providing products in a good yield. In the
case of compounds P15‐P23 and their derivatives, the presence of
Cbz protective group was required to improve the hydrophobicity of
the compounds, thus increasing their activity. As assumed, the
removal of the Cbz group resulted in the loss of these molecules' anti-
microbial activity.
bacteria as well as for Candida spp. grown in two different culture
media. Obtained results are presented in Tables 1 and 2.
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3
BIOLOGICAL ACTIVITY
Data presented in Table 1 indicate that some of the new compounds
showed moderate potency against Candida albicans, Escherichia coli,
and Staphylococcus aureus reference strains, with compounds 8a and
13a bearing FDMP residue being the most broadly active. The most
active against C. albicans ATCC 10231 was amphiphilic compound
19a, with four flexible arms terminated solely with amine groups.
Moreover, all compounds displayed much better activity against
New compounds were characterized by NMR and mass spectrum
analysis and their structures confirmed. Both free dendrimers and
their conjugates with FMDP were tested for the minimum inhibitory
concentration (MIC) against Gram‐positive and Gram‐negative

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STOLARSKA ET AL.
TABLE 1 Minimal inhibitory concentration (MIC) of the synthesized compounds and FMDP (μM)
Substituents
MIC, μM
RPMI 1640
MHB
MHB
Candida albicans ATCC
Escherichia coli ATCC
Staphylococcus aureus ATCC
Compound Charge
R
α‐Lys arm ε‐Lys arm 10231
25922
25925
+
+
+
8a
+4
CH2‐Ar
NH‐
FMDP
NH3
NH3
NH3
49
94
25
26
25
26
13a
+4
CH (CH3)
NH‐
FMDP
2
15a
18a
+4
+4
———
NH‐Cbz
79
159
585
39
NH‐
———
———
585
293
FMDP
+
19a
19b
+4
+4
———
———
NH‐Cbz
NH‐Cbz
NH3
15
249
357
31
NH‐
357
357
FMDP
+
21a
+2
+2
+1
Ser
NH‐Cbz
NH‐Cbz
———
NH3
145
150
>100
120
145
300
+
23a
But‐OH
———
NH3
FMDP
———
>500
>500
>500
tested strains than FMDP itself. The FMDP‐functionalized branched
peptides 8a and 13a were widely tested against the set of reference,
hospital‐acquired, and genetically modified Candida spp. strains grown
in two culture media. Fluconazole was used as a reference compound
(Table 2). The results of the experiment showed that the tested com-
pounds exhibited higher antifungal activity when grown in YNB‐SA
minimal medium than in rich, simulating physiological conditions RPMI
medium.
Collection of used Candida species included three wild strains, two
hospital‐acquired fluconazole‐sensitive strains (C. albicans B3‐ and C.
albicans Gu4‐) isolated from AIDS patients prior to initiation of anti-
fungal therapy, and two strains overproducing Cdr1p and Cdr2p (C.
albicans Gu5) or Mdr1p (C. albicans B4) pumps isolated from the same
patients after long‐term treatment with fluconazole.23 It should be
emphasized that both dendrimers 8a and 13a efficiently inhibited
the growth of both fluconazole‐insensitive strains grown in RPMI
medium.
TABLE 2 Antifungal potency of dendrimers 8a and 13a against
Candida spp. measured as minimal inhibitory concentration (MIC) in
two culture media
MIC, μM
Usually, peptides are mostly taken up by microorganisms via pep-
tide permeases. In our study analysis of results obtained for the C.
albicans SC5314 and its mutant C. albicans OPT indicated that the
transport of active compounds 8a and 13a may not be mediated by
peptide permease. These strains with knocked permease genes are
devoid of peptide permeases. Broad activity of dendrimers 8a and
13a, as well as a high antifungal potency of dendrimer 18a, suggests
that permeation of cell membrane by cationic dendrimers might be a
route of transport of the tested dendrimers into the cells. The hydro-
phobic dodecylamine (DDA) chains present in the dendrimeric struc-
tures may be incorporated into the microorganism membranes. More
conclusions could be drawn from experiments in which N‐
acetylglucosamine (NAG), a natural inhibitor of GlcN‐6‐P synthase,
was added toYNB‐SA medium. In case the enzyme GlcN‐6‐P synthase
was the only target for the tested 8a and 13a dendrimers, the addition
of NAG would result in the complete prevention of anticandidal activ-
ity. However, for the tested compounds, no such an effect was
observed, which suggests that GlcN‐6‐P synthase is not the only tar-
get for the new conjugates. It is important to point out that com-
pounds 8a and 13a showed activity also against fluconazole‐resistant
strain C. krusei.
YNB‐SA
RPMI 1640
Strain
8a 13a Fluconazole 8a 13a Fluconazole
Candida albicans
22 40
33 36
5.7
2.7
3.1
49 94
75 100
97 >100
38
5.6
25
ATCC 10231
Candida albicans S.
C5314
Candida albicans OPT 24 47
opt1‐
opt5Δptr2Δptr22Δ
Candida albicans B3
Candida albicans B4
36 32
27 29
5.7
75
80 >100
72 >100
79 89
92 98
22 26
88
>400
12
Candida albicans Gu4 34 37
Candida albicans Gu5 22 38
3.1
>400
22
>400
56
Staphylococcus
cerevisiae
11 19
Candida glabrata DSM 17 44
38
90 97
86 69
73 >100
50
11226
Candida krusei DSM
18 41
45 60
350
——
400
——
6128
Candida parapsilosis
DSM 5784
Fungal strains used to test antimicrobial activity:

STOLARSKA ET AL.
5 of 7
• C. albicans OPT opt1‐opt5Δptr2Δptr22Δ—Mutant of C. albicans
SC 5314 lacking peptide permeases,
fractions containing the title compound were collected and evapo-
rated to give conjugates as the light yellow oil.
• C. albicans SC5314—Wild strain, Collection of Gdansk University
of Technology,
•
C. albicans Gu4—Fluconazole‐sensitive, isolated from AIDS
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4.2
General method for the Boc deprotection
patient prior to initiation of therapy, initial for Gu5, University of
Wurzburg
The tert‐butoxycarbonyl protecting group was removed by treating
compounds with 4M HCl in dioxane (5 mL) for 4 hours, followed by
removing the solvent in vacuo. The products were triturated with
diethyl ether and after filtration, and the precipitate was dried in vacuo
over KOH.
• C. albicans Gu5—Isolated after long‐term treatment with flucon-
azole, overproducing Cdr1p and Cdr2p
• C. albicans ATCC 10231—Wild strain, American Collection
• C. albicans B3—sensitive to fluconazole, isolated from AIDS
patients prior to initiation of therapy, initial for B4, University of
Wurzburg
• C. albicans B4—Isolated from patient after long‐term treatment
with fluconazole, University of Wurzburg,
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4.3
General method for the Cbz deprotection
• S. cerevisiae ATCC 9763—Wild strain, American Collection
• C. glabrata DSM 11226—Wild strain, Collection of DSMZ,
• C. krusei DSM 6128—Wild strain, Collection of DSMZ,
• C. parapsilosis DSM 5784—Wild strain, Collection of DSMZ,
Cdr1p and Cdr2p pumps, University of Wurzburg.
The carboxybenzoxy protective group was removed by catalytic
hydrogenation of the compound dissolved in methanol in the presence
of a catalyst (5% Pd/C) followed by removing the solvent in vacuo.
The products were triturated with diethyl ether and were filtered
off. The precipitates were dried in vacuo over KOH.
(8a) C55H96N12O12*4HCl, M.W. 1259,24
MS (ESI, MeOH): m/z: 1136[M + Na]+
1H NMR (500 MHz, D2O), δ: 0.85 (m, 3H, CH3‐DDA), 1.2‐1.8 (m,
76H, β, γ, δ‐Lys, C2‐11‐DDA), 2.7‐3.1 (m, 20H, ε‐Lys, β‐Phe, C1‐
DDA), 2.85‐3.0 (m, 4H, CCHCH2‐FMDP), 3.9‐4.5 (m, 6H, α‐Lys, α‐
Phe, α‐FMDP), 6.7‐7.3 (m, 4H, CH¼CH‐FMDP), 7.15‐7.6 (m, 5H, Ar‐
Phe)
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4
CHEMISTRY
Thin layer chromatography (TLC) was performed on aluminum plates
(Kieselgel 60 F254, Merck) and compounds visualized by ultraviolet
(UV) light and crystalline iodine vapors (POCH). Adsorption column
chromatography was carried out using silica gel (70‐230 mesh, Merck),
(13a) C51H96N12O12*4HCl, M.W. 1211,19
MS (ESI, H2O): m/z: 1066[M + H]+
while the exclusion chromatography with
a Sephadex LH‐20,
1H NMR (500 MHz, D2O), δ: 0.7‐0.9 (m, 9H, CH3‐DDA, CH3‐Val),
1.3‐2.0 (m, 77H, β, γ, δ‐Lys, C2‐11‐DDA, β‐Val), 2.8‐3.2 (m, 18H, ε‐
Lys, C1‐DDA), 2.8‐3.1 (m, 4H, CCHCH2‐FMDP), 3.8‐4.5 (m, 6H, α‐
Lys, α‐Val, α‐FMDP), 6.5‐7.0 (m, 4H, CH¼CH‐FMDP)
Pharmacia Fine Chemicals. The MS spectra were recorded using
Agilent Technologies 6540 UDH Accurate‐Mass Q‐TOF and the
NMR spectra were recorded on Gemini Varian spectrometer operating
at 500 MHz using DMSO and D2O as solvents.
(15a) C74H116N14O14*4HCl, M.W. 1567,61
MS (ESI, H2O): m/z: 734[M + 2Na]2+, 1444[M + Na]+
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1H NMR (500 MHz, D2O), δ: 1.2 (s,12H, γ‐Lys), 1.4(m, 12H, δ‐Lys),
1.7 (m, 12H, β‐Lys), 2.2 (m, 12H, ε‐Lys), 3.1‐3.2 (m, 4H,
NHCH2CH2NH), 3.7‐4.3(m, 6H, α‐Lys), 5.3 (ss, 28H, CH2‐Ar, Ar)
(18a) C70H123N19O21*4HCl, M.W. 1708,65
MS (ESI, H2O): m/z: 544[M + 3Na]3+, 804,5[M + 2Na]2+, 1564[M +
H]+
1H NMR (500 MHz, DMSO), δ: 0.84(C12‐DDA), 1.23(C11‐DDA),
1.25(C6‐DDA), 1.31(C3‐DDA), 1.43(C10‐DDA), 1.68(C5‐DDA), 1.69
(C2‐DDA), 1.79(C4‐DDA), 2.3‐2.8(8H, NHCH2CO‐FMDP), 2.77(C8‐
DDA), 2.85‐3.65(32H, NCH2CH2CO, NHCH2CH2NH), 3.0‐3.6(8H, β,
γ, δ, ε‐Lys), 3.01(C7‐DDA), 3.12(C9‐DDA), 3.59(C1‐DDA), 3.6(α‐Lys),
3.63(12H, OMe), 3.65(4H, α‐FMDP), 6.86(8H, CH¼CH), 7.9‐9.2(12H,
NHCO), 8.45(4H, NH+‐FMDP), 10.17(NH‐C1‐DDA)
13C NMR (500 MHz, DMSO), δ: 14.4(C12‐DDA), 22.5(C11‐DDA),
25.0‐32.0(4C, NHCH2CO‐FMDP), 25.1(C5‐DDA), 25.2(C2‐DDA), 26.5
(C6‐DDA), 29.1(C10‐DDA), 30.5(C8‐DDA), 32.6(C3‐DDA), 32.8(C4‐
DDA), 33.0‐48.0(16C, NCH2CH2CO, NHCH2CH2NH), 36.0‐46.0(9C,
α, β, γ, δ, ε‐Lys, FMDP), 38.9(C9‐DDA), 40.0(C1‐DDA), 45.9(C7‐
4.1
General procedure for the preparation of
peptide dendrimers and conjugates
Peptide dendrimers were obtained using active esters method as
shown in Schemes 1 and 2. The substrate with free amino groups,
eg, 18, was dissolved in methanol, then 50% excess of corresponding
active ester in methanol was added successively. Reaction was carried
out at room temperature, intensively mixed for 3 to 5 days, progress
controlled by TLC, then the solvent was evaporated to dryness and
the postreaction mixture was dissolved in methanol. The compounds
were purified on Sephadex LH‐20 with methanol as mobile phase,
then the solvent was removed in vacuo to give the title derivatives.
Conjugates were obtained analogously using active esters method.
Peptide dendrimers with free amino groups were dissolved in metha-
nol, then 50% excess of Boc‐FMDP active ester in methanol was
added successively. After the reaction was completed (5 days), solvent
was evaporated, and the product was purified on a Sephadex LH‐20
column in methanol. The column was washed with methanol, and

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STOLARSKA ET AL.
DDA), 132.8(8C, CH¼CH), 165.0(4C, NHCOCH=CH), 169.0‐174.5(8C,
NHCO‐MA, NHCO‐MA), 170.9(4C, COOMe), 172.1(CO‐C1‐DDA)
(19a) C98H158N18O17*4HCl, M.W. 2006,25
MS (ESI, H2O): m/z: 981[M + 2H]2+, 953[M + 2Na]2+, 1861[M +
H]+
1H NMR (500 MHz, DMSO), δ: 0.85 (m, 3H, CH3‐DDA), 1.3‐1.4 (m,
82H, C (CH3)3,γ‐Lys), 1.45‐2.0 (m, 40H, β, δ‐Lys, C2‐11‐DDA), 2.5‐2.9
(m, 13H, ε‐Lys, C1‐DDA), 3.0‐3.8 (m, 32H, NHCH2CH2NH,
NCH2CH2CO), 3.85‐4.1 (m, 5H, α‐Lys), 6.5‐7.2 (m, 13H, NHCO), 7.1‐
8.0 (m, 12 H, NHCO)
fungal strains. The analysis of their antifungal properties indicates that
the examined molecules are efficient growth inhibitors of fluconazole‐
resistant hospital‐acquired strains. Moreover, application of amphi-
philic branched peptides such as FMDP carriers suggests that trans-
port mechanism involves more likely the cell membrane perturbation
than the mediation of the specific transport proteins.
ACKNOWLEDGEMENTS
This work was supported by the Faculty of Chemistry, Gdansk Univer-
sity of Technology, Gdansk, Poland, The Center for Advanced Studies
Project, Gdansk, Poland, and National Science Center: Opus 2012/07/
B/ST5/01941.
(19b) C130H198N26O33*4HCl, M.W. 2798,96
MS (ESI, H2O): m/z: 885[M + 3H]3+, 907[M + 3Na]3+, 1349[M +
2Na]2+
ORCID
1H NMR (500 MHz, DMSO), δ: 0.85 (m, 3H, CH3‐DDA), 1.3‐1.4 (m,
82H, C (CH3)3,γ‐Lys), 1.45‐2.0 (m, 40H, β, δ‐Lys, C2‐11‐DDA), 2.5‐2.9
(m, 13H, ε‐Lys, C1‐DDA), 3.0‐3.8 (m, 52H, CCHCH2‐FMDP,
NHCH2CH2NH, NCH2CH2CO, OCH3‐FMDP), 3.85‐4.1 (m, 9H, α‐
Lys, α‐FMDP), 6.5‐7.2 (m, 21H, CH¼CH‐FMDP, NHCO), 7.1‐8.0 (m,
12 H, NHCO)
Magdalena Stolarska https://orcid.org/0000-0001-7976-633X
Katarzyna Gucwa https://orcid.org/0000-0001-6750-3217
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5
CONCLUSION
A series of peptide dendrimers and their conjugates with an antifungal
agent FMDP were synthesized and tested. All compounds displayed
much better activity against the tested strains than FMDP itself. The
most promising molecules were tested against a broad selection of
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How to cite this article: Stolarska M, Gucwa K, Urbańczyk‐
Lipkowska Z, Andruszkiewicz R. Peptide dendrimers as anti-
fungal agents and carriers for potential antifungal agent—N3‐
(4‐methoxyfumaroyl)‐(S)‐2,3‐diaminopropanoic acid—synthesis
and antimicrobial activity. J Pep Sci. 2019;e3226. https://doi.
org/10.1002/psc.3226
19. Chandra S, Mayer M, Baeumner AJ. PAMAM dendrimers: a multifunc-
tional nanomaterial for ECL biosensors. Talanta. 2017;168:126‐129.
20. Luong D, Sau S, Kesharwani P. Iyer AK. Polyvalent folate‐dendrimer‐
coated iron oxide theranostic nanoparticles for simultaneous magnetic res-
onance imaging and precise cancer cell targeting Biomacromolecules.
2017;18(4):1197‐1209.